Together Against Melanoma: An Educational Symposium for Patients and Caregivers

Transcript

• 00:00Everyone?
• 00:02Everyone can hear okay in
• 00:03the back?
• 00:04Okay. Perfect. It's better than
• 00:06a Zoom call.
• 00:08So I just wanna thank
• 00:10every one of you who's
• 00:11come in the audience, many
• 00:13of whom we all know
• 00:14quite well.
• 00:16And it's always wonderful when
• 00:18people show up to support
• 00:20each other. And many of
• 00:21you have had very different
• 00:23journeys
• 00:24with us.
• 00:25We'll have time at the
• 00:26end for people to share,
• 00:28ask questions as well.
• 00:31You know, and tonight, I
• 00:32I think a lot of
• 00:33it is a night of
• 00:34celebration,
• 00:35for all of the things
• 00:37that have changed from the
• 00:38time that I was in
• 00:39training.
• 00:40I tell people all the
• 00:41time when I first started
• 00:43my journey,
• 00:44you know,
• 00:45as a family member of
• 00:47people who passed from melanoma,
• 00:49working on some of the
• 00:50things that won Nobel prizes
• 00:52and couldn't
• 00:54couldn't give it to a
• 00:55family member and where we've
• 00:56come
• 00:57in all of these years
• 00:59and that all of you,
• 01:01some of you who are
• 01:01in the audience were astronauts.
• 01:03You know, you
• 01:05there was a crazy ideas
• 01:07about immune therapy,
• 01:08and you guys went along
• 01:10for the ride. And not
• 01:11only that, but supported, you
• 01:13know, family members through the
• 01:15process.
• 01:16So on that note, thank
• 01:18you all. Debbie, I'm gonna
• 01:19you can
• 01:20make some opening remarks.
• 01:30Hello, everyone. I am Debbie
• 01:32Chergai. I am the senior
• 01:33education program manager at the
• 01:35MRF.
• 01:37We partnered today,
• 01:39with the ELF to put
• 01:40this symposium on for you
• 01:41today, so thank you so
• 01:42much for being here.
• 01:47First, I just wanna thank
• 01:48our sponsors.
• 01:50They these amazing companies have
• 01:52sponsored not only events like
• 01:54this, but they sponsor some
• 01:55of our other, many educational
• 01:57opportunities and events. In fact,
• 01:58if there's anyone here from
• 02:00any of these companies, is
• 02:01there, any industry reps here?
• 02:03Please raise your hands.
• 02:04Yes. Awesome. Take a look
• 02:06around. Thank them. Yes.
• 02:09Thank you so much
• 02:11for being here and for
• 02:12supporting events like this.
• 02:14Without their support, we truly
• 02:15could not do some things
• 02:17like this.
• 02:18First, I just wanna give
• 02:19a few facts.
• 02:21Some of you guys might
• 02:22know these already. In twenty
• 02:23twenty
• 02:24five, over two hundred and
• 02:26twelve thousand people. Oops. Sorry.
• 02:31There we go. People living
• 02:33in the United States are
• 02:34expected to be diagnosed with
• 02:35melanoma.
• 02:37Nearly ninety three percent of
• 02:38melanomas are thought to be
• 02:39caused by exposure to UV
• 02:41light and sunlight.
• 02:43Melanoma is not just a
• 02:44skin cancer, it develops anywhere
• 02:45in the body, eyes, nails,
• 02:47feet, mouth,
• 02:48and the five year survival
• 02:50rate for stage one to
• 02:51two localized melanoma is ninety
• 02:53seven point six percent.
• 02:55There are over one point
• 02:57four
• 02:57million people living with melanoma
• 02:59in the United States.
• 03:02And as I'm sure all
• 03:03of you know, melanoma is
• 03:04the deadliest form of skin
• 03:05cancer,
• 03:06and skin cancer is the
• 03:07most common form of cancer
• 03:09in the United States.
• 03:14The Melanoma Research Foundation is
• 03:16the largest independent organization
• 03:18devoted to melanoma,
• 03:20committed to the sport of
• 03:21medical research to develop effective
• 03:23treatments and eventually a cure
• 03:25for melanoma. I'm gonna give
• 03:26you just a short overview.
• 03:28I'll try to go quickly
• 03:29so we can get to
• 03:30the real amazing speakers today.
• 03:35This is our founder, Diana
• 03:36Ashby.
• 03:37She,
• 03:38MRF was founded in nineteen
• 03:40ninety six. She was diagnosed
• 03:41with melanoma and after a
• 03:43three year battle,
• 03:44found that there were no
• 03:45options for new therapies and
• 03:46clinical trials.
• 03:48A lot has changed since
• 03:49then.
• 03:52Diana's legacy lives through the
• 03:53MRF and all the incredible
• 03:55work we do. The MRF,
• 03:57we have three main, pillars,
• 03:59education, research, and advocacy.
• 04:01This is an example of
• 04:03one of our many educational
• 04:04events that we put on,
• 04:06and I'll go over just
• 04:07a few of the other
• 04:08things we have as well.
• 04:10A
• 04:11little bit of our footprint
• 04:12today. The MRF hosts several
• 04:14events all over the country
• 04:15including,
• 04:17nineteen,
• 04:19five k runs in different
• 04:20cities and states, two signature
• 04:22galas,
• 04:24and we bring patients and
• 04:25caregivers to DC
• 04:27to talk with congressional leaders
• 04:28about what is needed and
• 04:30why more funding is required
• 04:31for melanoma research.
• 04:36Research really is at the
• 04:37heart of our mission, supporting
• 04:39scientists whose discoveries lead to
• 04:41better treatments, improve outcomes, and
• 04:43new hope for melanoma patients.
• 04:46This slide highlights some of
• 04:47the groundbreaking research that MRF
• 04:49has funded in the past
• 04:50three in the past years
• 04:51and continues to support today.
• 04:53We have awarded thirty four
• 04:55grants,
• 04:56in two hundred and twenty
• 04:58five or sorry,
• 04:59twenty twenty five,
• 05:01and we've funded over twenty
• 05:02eight million dollars in research
• 05:04overall.
• 05:06This next slide,
• 05:09highlights some of the grants
• 05:10that we funded for Yale.
• 05:12So since two thousand eleven,
• 05:13the MRF has provided over
• 05:15nine hundred and fifty thousand
• 05:17dollars through nine grants
• 05:18to support the melanoma research
• 05:20at, at Yale. Through these
• 05:22grants, researchers
• 05:23have produced exciting results for
• 05:25the melanoma research community, including
• 05:28twelve
• 05:28scientific publications to advance the
• 05:31understanding of melanoma and its
• 05:32treatments.
• 05:34The MRF supported projects have
• 05:36also enabled Yale researchers to
• 05:38start over over forty new
• 05:40scientific collaborations and helped four
• 05:42Yale researchers
• 05:44secure additional funding from other
• 05:45sources to support their research.
• 05:52This is one of my
• 05:52favorite slides.
• 05:54Did you know that by
• 05:55funding melanoma research, you are
• 05:57also helping to advance
• 05:59all cancer research?
• 06:01Melanoma research breakthroughs have led
• 06:03to approvals in both targeted
• 06:04therapies for BRAF mutations
• 06:06and immunotherapy
• 06:08treatments
• 06:08for many cancers.
• 06:10Since the development of immunotherapy
• 06:12in the last ten years,
• 06:13distance
• 06:14metastatic disease patient survival rates
• 06:17increased
• 06:18from fifteen percent
• 06:19to over fifty percent.
• 06:21And as you can see
• 06:22in the slide, these are
• 06:23all the other,
• 06:25cancers that,
• 06:27you help by helping to
• 06:28fund melanoma research.
• 06:33Another facet of our research
• 06:34is our breakthrough consortium,
• 06:37which accelerates melanoma translational research
• 06:39through multi institutional collaborations and
• 06:42fostering the growth
• 06:44of early career scientists and
• 06:45clinical investigations.
• 06:47And as you can see,
• 06:48Yale University is on there.
• 06:52We have a variety of
• 06:53educational opportunities,
• 06:55not only directed at patients,
• 06:56but caregivers, providers.
• 06:58We have educational materials, webinars,
• 07:01animated patient videos,
• 07:03patient we give patient caregiver
• 07:04symposia like this, and we
• 07:06also have a lot of
• 07:07materials on rare subtypes.
• 07:11We have over thirty pieces
• 07:13of literature available on our
• 07:15website these are all free
• 07:17to download or order you
• 07:19can order bundles of them
• 07:20so if you have an
• 07:21educational event that you want,
• 07:24to bring some information to,
• 07:26I highly suggest
• 07:27going on our website, checking
• 07:29out our educational literature page,
• 07:30at the very end there's
• 07:31an order form,
• 07:33and you can order
• 07:34five hundred up to five
• 07:36hundred different types of or
• 07:37five hundred,
• 07:38materials
• 07:39for your events all for
• 07:41free.
• 07:42And you could do it
• 07:43multiple times a year.
• 07:49The melanoma the MRF also
• 07:51hosts monthly ask expert webinars.
• 07:54We have animated patient videos.
• 07:57These are great videos that
• 07:58are very short. They're about
• 08:00all less than ten minutes.
• 08:01They're a great way to
• 08:02share with people if you
• 08:04wanna educate them on, some
• 08:05of the,
• 08:06parts of melanoma,
• 08:08and we have some new
• 08:09ones in the
• 08:10works. And then also,
• 08:12if you want more education
• 08:13on our MRF YouTube channel,
• 08:16you can find all of
• 08:16our past patient and caregiver
• 08:18symposia. The one today will
• 08:19also be posted there in
• 08:21a week or two.
• 08:22All of our past, ASSA
• 08:24expert webinars, patient testimonials,
• 08:27and tons of other other
• 08:28things if you're looking for
• 08:29some more education.
• 08:32We also have an amazing
• 08:34patient and caregiver community.
• 08:36This, has been going on
• 08:37for many, many years, and
• 08:38so you can find so
• 08:39many different topics such as
• 08:41Till cell therapy, you know,
• 08:43new therapies,
• 08:44newly diagnosed patients who want
• 08:46some questions answered, bereavement
• 08:48support,
• 08:49there's so many different topics
• 08:51that you can search or
• 08:52you can start your own
• 08:53conversation.
• 08:57This is our new, program
• 08:59it's called SunAware.
• 09:00It's a sun safety e
• 09:02learning program for children in
• 09:03grades k through five.
• 09:05This curriculum promotes healthy sun
• 09:07safe habits to help prevent
• 09:09melanoma, skin cancer, and sun
• 09:10related skin damage.
• 09:12Right now, we are,
• 09:16circulating it through schools,
• 09:18and also youth organizations.
• 09:20If you guys want more
• 09:22information on it, for any
• 09:23of your local communities, please
• 09:25give us a contact.
• 09:30As I mentioned before every
• 09:31year we bring caregivers to
• 09:33the hill patients and caregivers
• 09:34to the hill to meet
• 09:35with state legislators and congressional
• 09:38leaders.
• 09:39We work with them to
• 09:40help increase funding for cancer
• 09:41and specifically melanoma research.
• 09:44If you would like to
• 09:45attend any of our, advocacy
• 09:47days, please contact us and
• 09:49we'll let you we'll let
• 09:50you know when the next
• 09:51one is.
• 09:54We have several prevention and
• 09:55awareness campaigns, included our get
• 09:57naked, I get dilated,
• 10:00Stay,
• 10:01Spot Stay Safe with Spot
• 10:03campaign with for pediatric melanoma
• 10:05awareness.
• 10:06Our twenty twenty six spokesperson
• 10:08is Jason Chambers. I don't
• 10:09know if any of you
• 10:10recognize him. He is a
• 10:12melanoma patient, superyacht captain in
• 10:15bravo below deck,
• 10:18down under star, and he
• 10:19is our new spokesperson this
• 10:21year.
• 10:24We also have several programs,
• 10:26that you can find more
• 10:27about on our website.
• 10:31And there are several opportunities
• 10:33if you're looking for ways
• 10:34to get involved. We have
• 10:35community fundraisers, galas, miles for
• 10:37melanoma walks. There there was
• 10:39a postcard for,
• 10:41a local one going on
• 10:43soon if you guys, on
• 10:44our table, if you're interested
• 10:46in attending.
• 10:49And lastly, the best way
• 10:50to learn more about anything
• 10:51that I mentioned here, any
• 10:52events that we have coming
• 10:53up, or anything in the
• 10:54future is to just follow
• 10:56us on social media. We're
• 10:57on on the major,
• 10:58channels.
• 11:02In your folders today or
• 11:04with your folders today, we
• 11:05also gave you a post
• 11:06event survey.
• 11:08There's also a QR code
• 11:10that you can scan at
• 11:11the MRF table. We would
• 11:12really appreciate you filling out
• 11:14this survey. You can fill
• 11:15it out today as you
• 11:16go along or you can
• 11:17do it and hand it
• 11:18to me as you leave
• 11:19or you can do it
• 11:20online later. We'll follow-up with
• 11:21an email with a link
• 11:22to the survey as well.
• 11:24It's a very short survey,
• 11:25but I promise you it's
• 11:27really important. It lets us
• 11:28know,
• 11:29you know, topics that you
• 11:31wanna hear more about, and
• 11:32it helps us create more
• 11:34events that are important to
• 11:35you.
• 11:38Lastly, I just wanna thank
• 11:39the sponsors again,
• 11:40for supporting events like this
• 11:42and for being here.
• 11:43And, of course, Yale New
• 11:45Haven Health, thank you so
• 11:46much for partnering with us
• 11:48today.
• 11:57So, before we actually start,
• 12:01with the the physicians here
• 12:03to give information, we actually
• 12:05wanted to have one of
• 12:06our patients who's had
• 12:08really quite the incredible journey.
• 12:11And if you wanna
• 12:14yep.
• 12:16Where do you want? You
• 12:16can go wherever you want.
• 12:18You're the star of the
• 12:19show.
• 12:20But come up here. Do
• 12:21you want a microphone and
• 12:22sit? Where'd you be comfortable?
• 12:23Okay. Here.
• 12:25Probably.
• 12:26Alright.
• 12:30And it's on. Okay. If
• 12:31it becomes too loud,
• 12:33just give me a signal.
• 12:35My name is Brandy Orton.
• 12:36I am,
• 12:38I'm married. I'm a mother
• 12:39of two children ages twelve
• 12:40and thirteen.
• 12:41My
• 12:42I have or had melanoma.
• 12:45Date my story dates back
• 12:46to
• 12:48people can't hear you? Okay.
• 12:49Okay. Is that better? Okay.
• 12:51Brandy Wharton,
• 12:53married, mother of two children.
• 12:54My melanoma story goes back
• 12:56to twenty nineteen, twenty twenty.
• 12:58I found a cut on
• 12:59my wrist, and what popped
• 13:00up a couple weeks later
• 13:01was something that looked almost
• 13:03like, a blister you get
• 13:04on the back of your
• 13:05heel. And at this point,
• 13:06I was forty years old.
• 13:07I'd had over thirty two
• 13:08basal cell carcinomas and several
• 13:10squamous cells. So I was
• 13:11very familiar
• 13:13with the dermatologist.
• 13:15I asked the dermatologist about
• 13:16that, and they said it
• 13:17was nothing, and then COVID
• 13:18hit. So I didn't go
• 13:19back to the dermatologist
• 13:21again until after the the
• 13:23majority of COVID had passed.
• 13:25When I did return, I'd
• 13:26asked about the spot again
• 13:27because it continued to grow,
• 13:28and they again told me
• 13:29it was nothing to worry
• 13:30about. They tried freezing it,
• 13:32and it grew very quickly.
• 13:33And, eventually, I had a
• 13:35biopsy and learned that it
• 13:36was melanoma.
• 13:37And in fact, I was
• 13:38told they believed it was
• 13:39a secondary cancer that, there
• 13:41was another type of cancer
• 13:42in my body. And during
• 13:43that time, I had over
• 13:44a month to wait for
• 13:45scans, so I really delved
• 13:46into a lot of I
• 13:48grew up in a natural
• 13:49focused household, so I dove
• 13:50into some of the research
• 13:52on naturopathic care and things
• 13:53I could do at home.
• 13:55We shifted to an organic
• 13:56diet and started juicing and
• 13:57taking some supplements.
• 13:59And then I found that
• 14:00the cancer luckily was not
• 14:01anywhere else in my body.
• 14:02I had a wide margin
• 14:03excision, and I thought that
• 14:04I was good to go
• 14:06and safe. I am an
• 14:07active duty service member, so
• 14:08I executed orders, and we
• 14:10moved to Tampa. And as
• 14:11part of my follow on
• 14:12care, we learned just a
• 14:13few months later that the
• 14:14cancer had, in fact, spread
• 14:16to the lymph nodes in
• 14:17my elbow.
• 14:18And so I met with
• 14:19the surgeon and with the
• 14:21oncologist,
• 14:22and I had a lot
• 14:22of questions. I'd done a
• 14:23lot of research. I had
• 14:24two young kids. I was
• 14:26very scared, and a lot
• 14:27of my questions were just
• 14:28brushed off. I felt unheard.
• 14:30I was told, hey. If
• 14:31you don't get treatment, you're
• 14:32gonna die, and they never
• 14:33answered my questions.
• 14:34I'd asked for a printout.
• 14:37They told me about the
• 14:38side effects of the treatment
• 14:39and statistics, and I was
• 14:41given a two page handout.
• 14:42And I left the doctor
• 14:43feeling very
• 14:45unfulfilled and very frustrated,
• 14:47and I thought there had
• 14:48to be a better way.
• 14:49So what it followed was
• 14:50a four year kind of
• 14:51journey where I tried a
• 14:52number of naturopathic things. I
• 14:54tried hyperbaric oxygen. I tried
• 14:55colon hydrotherapy. I tried lymphatic
• 14:57massage. I tried a number
• 14:59of diets and supplements, IVs,
• 15:01infrared saunas. But, ultimately, over
• 15:03the next four years, my
• 15:04cancer continued to grow until
• 15:06about September of twenty twenty
• 15:08four.
• 15:09I got follow on scans
• 15:10that showed it had spread
• 15:11to the lymph nodes in
• 15:12my in my, armpit, the
• 15:14axillary lobe. And I knew
• 15:16that that was a jumping
• 15:16off place to spread to
• 15:17other organs. And I was
• 15:18extremely scared because I was
• 15:20a, you know, a mother
• 15:22of two,
• 15:23with a wonderful career and
• 15:25a wonderful family, and I
• 15:26just was scared. I didn't
• 15:27know what to do, but
• 15:28I had been very frustrated
• 15:29by the interactions I'd had
• 15:31with the doctors up to
• 15:31that point. All of my
• 15:33concerns seemed to be brushed
• 15:34off,
• 15:35and none of my questions
• 15:36were answered. And I wasn't
• 15:37smart enough. I knew I
• 15:38wasn't smart enough to understand
• 15:40the medical,
• 15:41documents that I was reading.
• 15:43And so I felt very
• 15:44frustrated and kinda like I
• 15:45had nowhere to go.
• 15:46And, ultimately, I got a
• 15:48referral to Yale, and I
• 15:50met these two wonderful ladies.
• 15:51I met doctor Olena and
• 15:52doctor Kluger.
• 15:53And I will tell you
• 15:54that my experience was different
• 15:55at the get go.
• 15:57I got a call from
• 15:58nurse Rachel. She spent about
• 16:00thirty to forty five minutes
• 16:01on the phone asking me
• 16:02what had brought me here.
• 16:04I'd never had that before.
• 16:06I really felt heard, and
• 16:07I felt hopeful.
• 16:08And I went into the
• 16:10interactions with the doctors with
• 16:11a different kind of mindset
• 16:13just based off of that
• 16:14interaction.
• 16:15And then I met doctor
• 16:16Kluger, and I had a
• 16:17number of questions. And I
• 16:18actually warned nurse Rachel, like,
• 16:19hey. I ask a lot
• 16:20of questions. It's not because
• 16:21I'm trying to be I'm
• 16:22not trying to quiz the
• 16:23doctors. I'm genuinely curious. My
• 16:25life is at stake.
• 16:27I have questions that I
• 16:28need answered, and she welcomed
• 16:29the questions. And doctor Kluger
• 16:31answered every single one of
• 16:32those questions. Because at the
• 16:33same time as I was
• 16:34going through all these naturopathic,
• 16:36practices, I was still dialing
• 16:38into the AIM melanoma foundations,
• 16:40clinics that they would hold.
• 16:42I was keeping track of
• 16:43the research and trying to
• 16:44understand the studies that were
• 16:45coming out.
• 16:46And doctor Kluger was phenomenal.
• 16:48She answered every single one
• 16:49of my questions and was
• 16:50able to tell me why
• 16:51a certain,
• 16:52procedure or a certain treatment
• 16:54was not the ideal one
• 16:55for me or the additional
• 16:56risk that I held. And
• 16:57doctor Olena was wonderful. She
• 16:59came in, and she was
• 17:00very frank with me about
• 17:01the surgery and the potential
• 17:02side effects,
• 17:04but she was also very
• 17:04hopeful. And I left that
• 17:06doctor's appointment for the first
• 17:08time. I didn't cry leaving
• 17:09a doctor's appointment because usually
• 17:10I would I would have
• 17:11such anxiety and have such
• 17:12a bad experience that I'd
• 17:14be shaky and I would
• 17:15cry, and I left feeling
• 17:16hopeful.
• 17:18And that in conjunction with
• 17:19actually getting the full pamphlet
• 17:20of information,
• 17:22I read through it. I
• 17:23understood all the side effects.
• 17:24I felt fully informed enough
• 17:26to make a decision for
• 17:27my treatment for the first
• 17:28time, and that it's, you
• 17:29know, stemmed back to when
• 17:30I first learned I had
• 17:31cancer in January of twenty
• 17:33twenty one.
• 17:34That was incredible for me.
• 17:35That was a life changing
• 17:36experience.
• 17:37So I started immunotherapy.
• 17:39I had the double dose
• 17:40treatment.
• 17:41It started in November. We
• 17:42had planned a family trip
• 17:44to, Germany because it was
• 17:45my lifelong dream, and we
• 17:46weren't sure how much time
• 17:47I had because I was
• 17:48in pretty bad shape.
• 17:49We went to Germany. It
• 17:50was a rough trip,
• 17:52but I'm glad I went.
• 17:53And about a week before
• 17:54the second treatment,
• 17:56I was like, hey. I
• 17:57said to my husband, I
• 17:57think my tumor is shrinking.
• 17:59And he's like, yeah. Of
• 18:00course, it's shrinking. You know?
• 18:01He always had a positive
• 18:02mindset. He was always trying
• 18:03to be my cheerleader. And
• 18:05then, actually, the kind of
• 18:06reaffirming thing is my teenage
• 18:07daughter said, hey, mom. I
• 18:08think your tumor is smaller.
• 18:09And she hadn't heard me
• 18:10say anything, so I knew
• 18:11that, like, something was going
• 18:12on. And with that, no
• 18:14matter the side effects that
• 18:15I was experiencing, I was
• 18:16so hopeful. I was like,
• 18:17I can experience any side
• 18:18effects, and I will get
• 18:19through this because I'm seeing
• 18:20results.
• 18:21For the first time, I'm
• 18:22seeing results, and I just
• 18:24had such hope.
• 18:25So I did three doses
• 18:26of the double, double treatment.
• 18:29And then the decision was
• 18:30made by doctor Olino and
• 18:31doctor Kluger that it was
• 18:32time for surgery.
• 18:34I had surgery. And then
• 18:35a little while after my
• 18:36surgery, I learned that I
• 18:37had something called, I think,
• 18:38a complete response. Correct me
• 18:39if I'm wrong. Right? So
• 18:41my tumor had shrunk drastically,
• 18:43but what was what had
• 18:44remained had been completely killed
• 18:46by the treatments.
• 18:47I've continued with the single
• 18:49dose treatments,
• 18:50for good measure and because
• 18:51I did have some some,
• 18:52you know, enlargement in the
• 18:54lymph nodes up here. And,
• 18:56today, I had my second
• 18:57to last,
• 18:58immunotherapy treatment, and then I
• 19:00will be being monitored from
• 19:02here. So I just wanna
• 19:03say,
• 19:05I'm I'm thankful for my
• 19:07journey. I'm thankful for the
• 19:08things that I did to
• 19:09improve my overall health because
• 19:10I think they helped, you
• 19:11know, strengthen my immune system
• 19:13and set me up well
• 19:14for the surgery and the
• 19:15treatments that followed. But I
• 19:16am so extremely thankful for
• 19:18doctor Kluger
• 19:19and for doctor Olino
• 19:21for meeting me where I
• 19:22was at. And every patient
• 19:23is different. We all have
• 19:24our own journey, and we
• 19:25all need different things.
• 19:27I went to law school.
• 19:29I'm in the military. I'm
• 19:30trained to read everything to,
• 19:31you know, think critically, advise
• 19:33commanders on risk. So for
• 19:34me, I needed all the
• 19:36information to feel like I
• 19:37could make a well informed
• 19:38decision before I was comfortable.
• 19:40Some patients maybe don't need
• 19:41that. They don't wanna know
• 19:42because maybe it'll bring down
• 19:43their, you know, their mindset.
• 19:44They'll get scared, and they
• 19:45don't wanna know, and they
• 19:46just want that. And I
• 19:47was just so thankful that
• 19:48I finally found doctors who
• 19:49were able to meet me
• 19:50where I was at and
• 19:51make me feel comfortable enough
• 19:53to get the treatment that
• 19:53I needed. And I'm so
• 19:55incredibly hopeful for now the
• 19:57long life that I have
• 19:57ahead of me. Whereas less
• 19:59than six months ago, we
• 20:00were planning a final trip
• 20:01because we weren't sure if
• 20:02I was gonna make it.
• 20:03So thank you very much.
• 20:20That that I have a
• 20:21collection of that interaction for
• 20:23something completely different. See,
• 20:26I saw a lit you're
• 20:27a lieutenant. What's your rank?
• 20:28Walk into my office and
• 20:30tell me what was gonna
• 20:31happen. I didn't see an
• 20:32anxious lady who was nervous.
• 20:35Andy, I guess we just
• 20:36have a different read on
• 20:37that reality.
• 20:38Okay.
• 20:40That's why the surgeon got
• 20:42along really well with the
• 20:43military.
• 20:48Poor doctor Levinthal now has
• 20:50the unenviable
• 20:53to follow with this.
• 21:00Wow. I mean, that's really
• 21:01an inspiring story, and, thank
• 21:03you for sharing. And that's
• 21:04why we love what we
• 21:05do and being on our
• 21:06team here. So I'm John
• 21:08Leventhal. I'm a dermatologist at
• 21:10Smilo. I lead the Oncoderma
• 21:12Clinic. So I'm gonna get
• 21:13us started by going over
• 21:14many things that you probably
• 21:15already know, the diagnosis, risk
• 21:17factors, prevention, and screening of
• 21:19melanoma.
• 21:20You already heard a few
• 21:21key facts earlier, but skin
• 21:22cancer is the number one
• 21:24cancer in the United States.
• 21:26Melanoma is the fifth most
• 21:27common. And while basal cell
• 21:29and squamous account for the
• 21:30majority, melanoma is the deadliest
• 21:32form
• 21:33and,
• 21:34over a million people live
• 21:35with it, and we see
• 21:36it every day. So what
• 21:37is melanoma? Melanoma is specifically
• 21:39a tumor, a cancer of
• 21:41the cells that give our
• 21:42body pigment. Those are called
• 21:43melanocytes.
• 21:45And most cases occur on
• 21:46the skin in areas that
• 21:48are completely normal and then
• 21:49just develop. Some melanomas occur
• 21:52from an atypical birthmark or
• 21:54a mole that changes over
• 21:55time.
• 21:56So who develops melanoma?
• 21:58Anyone can develop melanoma. I
• 22:00have patients who are young,
• 22:02over a hundred, all genders,
• 22:04ethnicities.
• 22:05The majority of people statistically
• 22:07are older white men over
• 22:09age fifty. Under age fifty,
• 22:11more women than men tend
• 22:12to have melanoma probably due
• 22:14to tanning habits, but by
• 22:15age
• 22:16sixty five plus, more men
• 22:17have it than women.
• 22:18And as you can see
• 22:19in this chart, it's really
• 22:21incredible. The lifetime risk in
• 22:22the United States has dramatically
• 22:24increased over the past decades.
• 22:26And currently, it's probably about
• 22:28one in,
• 22:29probably,
• 22:30forty has happened in two
• 22:32thousand twenty six.
• 22:33So let's go over melanoma.
• 22:35So
• 22:36what do we do to
• 22:37diagnose it? So step one
• 22:38and the most important step,
• 22:39well, some of these
• 22:41slides aren't coming out, but
• 22:42that's okay, is identifying
• 22:44a concerning lesion, and that's
• 22:46really the most important step
• 22:47here. So we have to
• 22:48know what does melanoma
• 22:50look like.
• 22:52So it's very important to
• 22:53go over the a, b,
• 22:54c, d, e's. You're You're
• 22:55probably familiar with it. A,
• 22:56asymmetrical.
• 22:58B, the border's irregular. C,
• 23:00the color is varied.
• 23:01D, I don't like diameter
• 23:03pencil tip eraser because I've
• 23:04diagnosed some teeny tiny melanomas.
• 23:06So I prefer dark because
• 23:08the vast majority of melanomas
• 23:09that I find are dark.
• 23:11Not not all of them,
• 23:11but most of them. And
• 23:13e is probably the most
• 23:14important one, and that's evolution.
• 23:16So the lesion
• 23:17changes in any way, and
• 23:18patients are really good at
• 23:20coming in and saying, you
• 23:21know, doc? Something's a little
• 23:22bit different about this mole.
• 23:23And trusting that patient intuition
• 23:25is really key.
• 23:27And so what do melanomas
• 23:28look like? So the superficial
• 23:30spreading, these are the most
• 23:31common types of melanomas. They're
• 23:33atypical pigmented lesions. You can
• 23:35see these are some really
• 23:36classic ones that are pretty
• 23:37tough to miss. Right? They
• 23:38really obey all the a,
• 23:40b, c, d, e rules.
• 23:41Nodular melanomas,
• 23:43this is a kind of
• 23:44an aggressive type. They grow
• 23:45fast. Patients will come in
• 23:47and say, this thing just
• 23:48showed up a few months
• 23:49ago. It's growing really fast.
• 23:50These are the ones that
• 23:52you can't just wait for
• 23:53your yearly dermatology visit because
• 23:55you're gonna come in with
• 23:56a thick melanoma.
• 23:57Lentigo maligna, we see these
• 23:59in mostly elderly patients with
• 24:01lots of lentigos. Those are
• 24:02sunspots, and these melanomas arise
• 24:04in these in these chronic
• 24:06sun damaged areas. Now amelanotic,
• 24:08this is always a tough
• 24:10one. And I have a
• 24:10lot of patients that will
• 24:11come in and say,
• 24:12my dermatologist,
• 24:14you know, before seeing you
• 24:15thought it was a pimple.
• 24:16It was pink. It wasn't
• 24:17dark. They thought it was
• 24:18a basal cell. So these
• 24:20are not the most common
• 24:21presentations, but we see these.
• 24:23So this is kind of
• 24:23the rule I was mentioning
• 24:24earlier. If there's something on
• 24:26your skin that's changing, evolving,
• 24:27just doesn't seem right to
• 24:28you, a sore that's not
• 24:29healing, you should see a
• 24:30dermatologist.
• 24:31And then there's the melanomas
• 24:33that don't happen in areas
• 24:34with sun. They happen on
• 24:35the palms, the soles, under
• 24:37the nails. These are called
• 24:38aqual indigenous, and we see
• 24:40these predominantly in patients with
• 24:42darker skin types, but not
• 24:43always. The nail band melanoma,
• 24:46it it starts in the
• 24:47nail matrix, and it grows
• 24:49upward like a black band.
• 24:50So many of my patients,
• 24:52after seeing this talk, come
• 24:53in with a little blood
• 24:54spot under their nail and
• 24:55say, doc, I have melanoma.
• 24:56No. So not like a
• 24:57little red streak of blood,
• 24:58but a dark pigmented lesion
• 25:00that's a band in the
• 25:01nail fold.
• 25:02So
• 25:03what do we do next?
• 25:04We we obtain a skin
• 25:05biopsy. That's step two. And
• 25:07this is really easy for
• 25:08dermatologists to do. I could
• 25:10do it in thirty seconds
• 25:11probably. It just takes a
• 25:12couple minutes. And the type
• 25:14of biopsy is really not
• 25:15that important. Most of the
• 25:16time, we do a shave
• 25:17biopsy. But the important thing
• 25:19is having it read by
• 25:20a good pathologist. We have
• 25:21the best pathologist in the
• 25:22world here at Yale, and
• 25:24they're able to make the
• 25:25diagnosis.
• 25:26And the pathologist will also
• 25:27tell you how thick the
• 25:28melanoma tumor is, which is
• 25:30such an important,
• 25:31determinant
• 25:33of how of of survival
• 25:35prognosis.
• 25:36Majority of melanomas are thin
• 25:38stage one. Patients have, you
• 25:39know, close to ninety nine
• 25:40percent survival, good outcomes.
• 25:43So let's keep moving. So
• 25:44next is risk factors and
• 25:46prevention.
• 25:47So like any cancer,
• 25:49melanoma has,
• 25:50risk factors that are environmental,
• 25:53that we can modify, and
• 25:54has risk factors that are
• 25:55genetic
• 25:56and that we cannot, prevent.
• 25:59Sorry some of these slides
• 26:00didn't come out when, I
• 26:01sent the email. So this
• 26:03slide is showing you, you
• 26:05can guess what's in the
• 26:05middle, ultraviolet radiation from the
• 26:07sun. So that's the number
• 26:09one risk factor. So ultraviolet
• 26:11radiation hits the Earth's surface.
• 26:13Ultraviolet c is pretty much
• 26:14blocked by the ozone, but
• 26:16UVA and UVB penetrate the
• 26:18Earth's surface. UVA can also
• 26:20penetrate car glass windows. And
• 26:22what happens is these ultraviolet
• 26:23rays from the sun cause
• 26:25damage in our DNA in
• 26:26the skin, and as the
• 26:28DNA damage mutations,
• 26:30over time,
• 26:32develop,
• 26:33skin cancer
• 26:35forms. And, unfortunately,
• 26:36the type of ultraviolet exposure
• 26:38that is
• 26:40the most detrimental
• 26:41is the type we love
• 26:42the most. You know, sunny
• 26:44vacations at the beach, short,
• 26:45intense bursts of ultraviolet. And
• 26:48the majority of melanomas are
• 26:50attributed to to,
• 26:51ultraviolet radiation.
• 26:53And we know that sunburns
• 26:54in childhood matter a lot,
• 26:56but it's really the data
• 26:57shows it's cumulative sunburns. I
• 26:59have many patients that say,
• 27:00doc, I'm probably already in
• 27:02trouble. I burned a lot.
• 27:03I should just live out
• 27:04my life and enjoy myself
• 27:05in the sun. I say,
• 27:06yes. Your childhood sunburns hurt
• 27:08you, but we know from
• 27:09the data it's really cumulative
• 27:11sun damage. So you can
• 27:13reduce the total burden of
• 27:14ultraviolet damage. You can reduce
• 27:16the future risk of developing
• 27:18melanoma.
• 27:18We also know that tanning
• 27:20beds are a major risk
• 27:22factor.
• 27:22Studies have shown that young
• 27:24women in particular,
• 27:26they did a study, had
• 27:27a six fold increased risk
• 27:28of developing melanoma. In Connecticut,
• 27:30it's actually banned now, indoor
• 27:31tanning for minors. Many states,
• 27:34minors can still do indoor
• 27:35tanning beds.
• 27:36A question I get asked
• 27:37a lot. What about spray
• 27:38tan? Is that gonna cause
• 27:40melanoma?
• 27:40So spray tanning is okay.
• 27:42You just don't wanna overdo
• 27:43it and look like a
• 27:44carrot, like Ross from Friends.
• 27:46But spray tanning is fine.
• 27:48So let's go over the
• 27:49risk factors that we,
• 27:51can change. These are these
• 27:52are the genetic risk factors.
• 27:53And, again, my apologies about
• 27:55the slides, but having over
• 27:57a hundred moles is a
• 27:58risk factor. Having atypical moles,
• 28:01having lots of sunspots, all
• 28:03of these are risk factors
• 28:04for developing melanoma.
• 28:05And you can see the
• 28:06difference between,
• 28:08skin that has never seen
• 28:09the sun
• 28:10versus skin that has seen
• 28:11the sun underneath, all these,
• 28:13sunspots and formation of, these
• 28:15these these lentigels, we call
• 28:17them. We also know that
• 28:18having light skin, light hair,
• 28:20blue eyes, freckles, all of
• 28:21that increases a risk of
• 28:22melanoma.
• 28:23And a lot of our
• 28:24patients with melanoma have these
• 28:25risk factors.
• 28:26So if you look in
• 28:27the mirror and if you
• 28:28look a little bit like
• 28:29Julianne Moore, which is a
• 28:30great thing, you should be
• 28:31ultra, you know, protective of
• 28:32yourself in the sun.
• 28:34And then there's genetics, and
• 28:35we can change our genetics.
• 28:37Right? But it's important to
• 28:38know about it. If you've
• 28:39had a skin cancer, you
• 28:41have an increased risk of
• 28:41getting melanoma. You have a
• 28:43forty percent lifetime risk of
• 28:44getting another skin cancer if
• 28:46you've had a melanoma. If
• 28:47you have a first degree
• 28:48relative with melanoma,
• 28:49it doubles your risk. And
• 28:51we know that there's genetic
• 28:52syndromes, and I have some
• 28:53of these patients in my
• 28:54practice
• 28:55where genes get passed on
• 28:56from generation to generation, and
• 28:58there's a very strong family
• 28:59history of melanoma
• 29:00and other cancers like pancreatic
• 29:02cancer. And so I always
• 29:03go by the rule of
• 29:04threes. If you've had three
• 29:06melanomas personally
• 29:07or if you know three
• 29:08first degree relatives in your
• 29:10family that had melanoma or
• 29:11pancreatic,
• 29:12ask your doctor about genetic
• 29:14testing.
• 29:17And then finally,
• 29:18prevention.
• 29:19So we know ultraviolet radiation
• 29:21is the number one modifiable
• 29:22risk factor. Right? So avoid
• 29:24tanning, protect yourself in the
• 29:25sun. I get asked a
• 29:27thousand times a day, well,
• 29:28what sunscreen should I use?
• 29:29My patients bring in, like,
• 29:30twenty of them, and they're
• 29:31so concerned with which one
• 29:32to use. They're not using
• 29:33any of them. And I
• 29:34say, we need to simplify
• 29:35this. Okay?
• 29:37The best sunscreen is the
• 29:38one that you're gonna use.
• 29:40SPF thirty and above, the
• 29:41data shows that's really probably
• 29:43the number you need. Anything
• 29:45above that, like SPF a
• 29:46hundred, is much more expensive
• 29:47and probably doesn't give you
• 29:48a whole lot more benefit.
• 29:49But SPF thirty and above,
• 29:51that's what you're aiming for.
• 29:52Reapplying it every few hours
• 29:54when you're outdoors. I mean,
• 29:55that's really the big thing.
• 29:56Wearing a hat, sun protective
• 29:58clothing, and just using common
• 30:00sense. You can still enjoy
• 30:01your summer, but you should
• 30:02protect your skin. Then the
• 30:04last part of the talk
• 30:05are what can dermatologists do,
• 30:07and is screening important?
• 30:10So the United States Preventative
• 30:11Services Task Force, they say
• 30:13that not everyone on the
• 30:14planet needs a dermatologist
• 30:16for skin cancer screening.
• 30:18There's too many people. And
• 30:19so what we do is
• 30:21we don't recommend that everyone
• 30:22should be screened. But if
• 30:24you are an at risk
• 30:25individual, then you should. If
• 30:26you've had skin cancer before,
• 30:28if if you have a
• 30:28strong family history, if you
• 30:30look in the mirror and
• 30:31you're covered in atypical moles
• 30:32and hundreds of moles, you're
• 30:33someone who should see a
• 30:34dermatologist.
• 30:36Definitely see a dermatologist who's
• 30:37gonna do a thorough total
• 30:38body skin exam.
• 30:40Does not take a long
• 30:41time, but you can still
• 30:42be very thorough in a
• 30:43short amount of time. A
• 30:44dermatologist that looks at you
• 30:45from across the room is
• 30:46not the one that you
• 30:47should be seeing for a
• 30:48skin check.
• 30:49And youth education programs like
• 30:52we spoke about earlier, really
• 30:53important.
• 30:54And so the evidence has
• 30:56shown that dermatologists
• 30:57find melanoma tumors that are
• 30:59thin, thinner than the general
• 31:00population, thinner than primary care
• 31:02doctors, and so we know
• 31:03the thickness is super important.
• 31:05Picking up a thin melanoma
• 31:07earlier on is crucial. And
• 31:09we also know from studies
• 31:10that patients can be taught
• 31:11what to look for, doing
• 31:12skin checks, looking in the
• 31:14mirror every month or so.
• 31:15And so I always like
• 31:16to tell patients, look for
• 31:18the ugly duckling sign. Look
• 31:19for something on your skin
• 31:20that's different
• 31:22from other moles, changing. That's
• 31:24something you should bring to
• 31:25my attention. Don't wait if
• 31:26it develops a month after
• 31:27hour visit for our yearly
• 31:29skin check.
• 31:31What can we use as
• 31:32dermatologists? So we have certain
• 31:33tools.
• 31:34My patients know I don't
• 31:35I don't go anywhere without
• 31:36my dermatoscope, my dermlight. It's
• 31:38a magnifying lens. It allows
• 31:40us to look at them
• 31:40all, which should the naked
• 31:41eye might seem okay. But
• 31:43then with my dermlight, I
• 31:44might see some pigment changes
• 31:45that are abnormal, so I'll
• 31:47take a skin biopsy. So
• 31:48we all use dermatoscope.
• 31:50We sometimes do digital photography.
• 31:52I have some patients that
• 31:53are covered in atypical moles.
• 31:54We'll take photos and look
• 31:55over time. I still think
• 31:57the patient doctor interaction is
• 31:59more important than some new
• 32:01AI tool saying that something
• 32:03may have changed because some
• 32:04changes are okay.
• 32:06And then finally, I'll end
• 32:07by saying,
• 32:09advocate for yourself and your
• 32:10skin. Do do monthly or
• 32:11every couple months skin checks
• 32:13on yourself or your partners.
• 32:14All you need is a
• 32:16mirror and a handheld mirror,
• 32:17and I have a little
• 32:18demonstration here.
• 32:20Let's
• 32:23see.
• 32:33But it's can't like it.
• 32:45Look in the scalp,
• 32:47try to spread the toes,
• 32:49gotta look in the buttock,
• 32:51look in the areas,
• 32:53look in the sun, look
• 32:55in the mouth to purr
• 32:55on the back.
• 33:00So a nice thorough skin
• 33:01exam. So with that, I'll
• 33:02end, and I look forward
• 33:03to taking questions later. Thank
• 33:05you.
• 33:19Just a little shorter than
• 33:20doctor Leventhal.
• 33:23So I'm gonna talk about
• 33:24something that's been a real
• 33:25paradigm
• 33:26shift pretty much in the
• 33:27last five years and really,
• 33:28you know, highlights,
• 33:30the journey that that Brandy
• 33:31spoke a little bit about,
• 33:32and and that's the the
• 33:33shift towards what we call
• 33:34neoadjuvant
• 33:35therapy.
• 33:37So, again, historically, we talk
• 33:39about removing the skin, removing
• 33:42lymph nodes. Some of you
• 33:43may have had what we
• 33:44call a wide local excision
• 33:45and a sentinel node biopsy
• 33:46that are in the audience.
• 33:49But,
• 33:50you know, unfortunately, melanoma could
• 33:52spread to other locations. And,
• 33:54again, in the time before
• 33:55we had immune therapy,
• 33:58people sometimes had locations surgeons
• 34:00could remove and some of
• 34:01them did very well and
• 34:02others didn't have that same
• 34:04outcome.
• 34:06And again, here, lymph nodes,
• 34:08lots of people did pretty
• 34:09well. Lung, not so well.
• 34:11Other places.
• 34:12Right? This is again where
• 34:13we started from when we
• 34:15had hopes and prayers and
• 34:16surgery and not much else.
• 34:18And then again, many of
• 34:20you in the room may
• 34:20have received or have now
• 34:22heard about
• 34:23what was
• 34:24practice changing, Nobel Prize winning
• 34:27work,
• 34:29that
• 34:30came into clinical trials. And
• 34:32melanoma was one of the
• 34:33first fields
• 34:34actually to study this and
• 34:37patients, again, some of you
• 34:38that are even in the
• 34:38audience today, some of the
• 34:39first people who received this,
• 34:41actually received it at Yale.
• 34:45And with this, people again,
• 34:46the old paradigm was
• 34:48after surgery. So, again, someone
• 34:50would show up. They'd have
• 34:51tumors in locations. We take
• 34:53them out, particularly if they
• 34:54were in the lymph nodes,
• 34:55and then we would give
• 34:56people immune therapy. And people
• 34:58started saying this. Is this
• 35:00the best way to go
• 35:01about this? You know, scientifically,
• 35:03does this make
• 35:04sense?
• 35:05Right? So, you know, as
• 35:06with everything, we want to
• 35:07say, what are we doing?
• 35:09This has been successful, but
• 35:11how can we improve upon
• 35:12it? How can we learn
• 35:13more? How can we do
• 35:14better?
• 35:16So
• 35:17again, particularly in patients who
• 35:19had melanoma that we could
• 35:21feel, you know, areas in
• 35:23the the lymph nodes,
• 35:25places that we could see,
• 35:26areas in the skin, we
• 35:27call those in transits.
• 35:29And then also certain places
• 35:30where you could remove something
• 35:32with an operation, but maybe
• 35:34it wasn't an emergency.
• 35:35Sometimes a spot in the
• 35:36lung, a spot in the
• 35:37bowel.
• 35:39And
• 35:40why did we think that?
• 35:41Again, if you kind of
• 35:42think, you know, like a
• 35:43scientist and a doctor, you
• 35:45know.
• 35:46But again, a lot of
• 35:47common sense. If you have
• 35:48something in place and you
• 35:49give someone a treatment,
• 35:51you can kind of see
• 35:52what it's how it's working.
• 35:53Right? It shrinks.
• 35:54You know, Brandy had that
• 35:56experience.
• 35:57Sometimes, again, when it shrinks,
• 35:58it makes your operation
• 36:00safer to do. So if
• 36:01it works, you know, that's
• 36:02a good reason to do
• 36:03this.
• 36:04If we look at our
• 36:05immune system,
• 36:06again, if the target's in
• 36:08place, there's some thought that
• 36:09maybe we get a better
• 36:10variety of t cells that
• 36:12are surrounding the tumor that
• 36:14may persist longer even after
• 36:16the tumor is removed.
• 36:19And, again, for learning for
• 36:21the next patient, you know,
• 36:22for the next trial too,
• 36:24we learn every single time
• 36:25that we have a response
• 36:27or we don't have a
• 36:28response
• 36:29from our patients and from
• 36:30the samples that are that
• 36:31are garnered from that. And
• 36:33the other thing too is,
• 36:34you know, there's nothing worse,
• 36:35you know, particularly being the
• 36:36surgeon,
• 36:37then you do a a
• 36:39big operation.
• 36:40You think you help someone,
• 36:42and man, the melanoma
• 36:44is back. Right? And you
• 36:45say, did we miss an
• 36:46opportunity to maybe treat that
• 36:48person earlier with something that
• 36:49would be more effective?
• 36:53So again, this is just
• 36:54a little cartoon illustration of
• 36:56kind of a little bit
• 36:57more of that that concept
• 36:59of having these different t
• 37:01cells in the area. You
• 37:02know, if we take that
• 37:03out first,
• 37:04there's less for the immune
• 37:06system to recognize. So people
• 37:07were really saying, you know,
• 37:10what order should we do
• 37:11this at?
• 37:13So,
• 37:14again, one of the first
• 37:15thing was kind of the
• 37:16double therapy that that Brandy
• 37:18had talked to a little
• 37:19bit. And this was some
• 37:20of the early studies trying
• 37:21to say, okay, how do
• 37:22we get the right combination?
• 37:24One that we don't want
• 37:25to be too toxic,
• 37:27but one that we want
• 37:28to work. Right? Because we
• 37:29always balance. What is the
• 37:30treatment due to the tumor
• 37:32and what does it do
• 37:33to our patient? Right?
• 37:34Both are important.
• 37:38So this was kind of
• 37:39the the winner that then
• 37:40went through to the next
• 37:41round of trials.
• 37:44And we also said too,
• 37:45again, could we just do
• 37:46a single? Right. So this
• 37:48is what this was what
• 37:49we call the swab trial.
• 37:50That was the organization that
• 37:51did that did this across
• 37:53patients. This is just with
• 37:54a single type of immune
• 37:55therapy.
• 37:56Seeing a difference between in
• 37:58blue, the people who got
• 37:59immune therapy before surgery, the
• 38:01red are people who had
• 38:03surgery and then had the
• 38:04immune therapy,
• 38:05and seeing some responses.
• 38:08We think probably the doublet,
• 38:10you know, maybe a little
• 38:11bit stronger,
• 38:12but it's also got more
• 38:14side effects. But again, this
• 38:15is a big trial that
• 38:16was done called the Nadina
• 38:18trial. And it also said,
• 38:20why don't we learn
• 38:21from what the tumor does?
• 38:23Do we need to do
• 38:25you know, what kind of
• 38:26an operation do we need
• 38:27to do? Do we need
• 38:28to give people more treatment
• 38:30after? Right? So, you know,
• 38:32in in in our best
• 38:33circumstances, you know, if we
• 38:34give someone a therapy
• 38:36and
• 38:37the pathologist
• 38:38examines it and says all
• 38:39the melanoma's dead and been
• 38:40replaced,
• 38:41do they need to get
• 38:42more treatment? Right? So these
• 38:43are all of the things
• 38:44because, again, the treatments can
• 38:46have side effects. We don't
• 38:47know when they'll come. Some
• 38:48people will never get them.
• 38:49Sometimes they'll get them late.
• 38:51Right? So everything we say,
• 38:52okay. How can we be
• 38:53smarter about what we're doing?
• 38:56So again, in this again
• 38:57again in blue, the people
• 38:58who got the doublet
• 39:00immune therapy first. Right? That's
• 39:02the blue line. The red
• 39:04line under there. And when
• 39:05we look at, you know,
• 39:07did something happen?
• 39:08Was there an event that
• 39:09a tumor come back or
• 39:11not? You know, you see,
• 39:12you know, lasting, you know,
• 39:14almost to about three years,
• 39:16you know, there were people
• 39:17who had really, really good
• 39:18responses.
• 39:19And the thing that becomes
• 39:20actually the most important is
• 39:22when we break it down
• 39:23by
• 39:24in people who
• 39:25when the pathologist examined it
• 39:27and they had what we
• 39:28called a major pathologic response.
• 39:30Right? They examined. They said,
• 39:31man, this immune therapy took
• 39:33care of the tumor.
• 39:35The number of people that
• 39:36the melanoma then came back
• 39:37later
• 39:38was actually a rarer event.
• 39:40And again, this is kind
• 39:41of what we we talk
• 39:42about, you know, evolving, cutting
• 39:45edge. You know, it's taken
• 39:46many years to get there
• 39:48since the first trials.
• 39:50And we, again, we do
• 39:51worry. Right? We do worry
• 39:53if someone gets a a
• 39:54side effect as well. And,
• 39:56you know, even though we're
• 39:57we're intending to shrink the
• 39:59tumor and maybe having a
• 40:00good response,
• 40:01but, again, not everyone
• 40:03is gonna have a great
• 40:04response.
• 40:06And we're finding that out
• 40:07earlier too, so we can
• 40:08start thinking about what's the
• 40:10next thing. Okay. And that
• 40:11also becomes important and valuable.
• 40:16So just to to conclude,
• 40:18you know, there's other
• 40:19types of recipes that are
• 40:21being investigated.
• 40:22Right. So there's another type
• 40:24that some people here may
• 40:25have been exposed to something
• 40:27called lag three. There's a
• 40:28couple of different companies with
• 40:30different versions
• 40:31that's ongoing to see is
• 40:33that a better balance between
• 40:34getting a good response and
• 40:36less side effect.
• 40:38There's gonna be a big
• 40:39study that changed even how
• 40:41we manage people's lymph nodes.
• 40:43And now in the setting
• 40:44of people who have lymph
• 40:45nodes that we can feel,
• 40:46they get therapy.
• 40:48As a surgeon, do I
• 40:49have to take them all
• 40:49out?
• 40:50Am I are you gonna
• 40:51live longer and live better
• 40:53if I do that?
• 40:54Or
• 40:55maybe if you started with
• 40:56one or two, do I
• 40:57just take the ones that
• 40:58we know and we leave
• 40:59the rest of the lymph
• 40:59nodes? Almost what I do
• 41:01when I do a central
• 41:02node biopsy on folks.
• 41:04There's other blood markers again
• 41:05that people may be hearing
• 41:07a little bit about. I
• 41:08don't know if doctor Tran
• 41:09or doctor Ishizuko mentioned that
• 41:11things like circulating tumor DNA,
• 41:13complementary
• 41:14blood tests that may help
• 41:15us detect things and to
• 41:17say, well, if we see
• 41:18this combination,
• 41:19maybe we should continue to
• 41:21give people treatment, things that
• 41:22we learn, things that we
• 41:24adapt to by the knowledge
• 41:25that we garner.
• 41:26Probably the most important thing
• 41:28is the people who are
• 41:29not responding.
• 41:30What should we do for
• 41:31them? Right. So that's why
• 41:33when we're all done working
• 41:34in clinic, all of us
• 41:35go to the lab and
• 41:36we say, what what's the
• 41:38next thing that we can
• 41:39do and why we at
• 41:40our meetings that everyone's working
• 41:41hard to think about? What
• 41:42do we do for the
• 41:43people we can't help right
• 41:44now?
• 41:45Should we do it in
• 41:46people who have bad melanomas
• 41:48that don't go to lymph
• 41:50nodes that start in the
• 41:51skin that are just big
• 41:52and aggressive and we're worried
• 41:54about them?
• 41:55That's some of the things
• 41:56that are being studied.
• 41:57And again, with everything we
• 41:59wanna figure out as the
• 42:00earliest point
• 42:02whether things are responding.
• 42:04Right? Because those are the
• 42:05people we wanna continue. And
• 42:06again, if we can figure
• 42:07that out, we wanna stop
• 42:09a therapy that's not helping.
• 42:10Right? Because then we're only
• 42:11causing potential harm and not
• 42:14good.
• 42:15So
• 42:17with that, I will leave
• 42:18you with my favorite cartoon.
• 42:28Alright.
• 42:29As usual, I speak fast.
• 42:31So doctor Tran
• 42:38Kinda wish I had cartoons
• 42:40and
• 42:41pet videos now that again
• 42:43so I'm gonna kinda dovetail
• 42:45along to what doctor Alino
• 42:47had already started. We're gonna
• 42:48be talking about systemic therapies
• 42:50and how we think about
• 42:51treating advanced melanomas.
• 42:53I think one of the
• 42:54main takeaways that I want
• 42:56to familiarize everyone with tonight
• 42:58is a lot of these
• 42:59drugs that you may have
• 43:00heard about on the news
• 43:02or in clinic from your
• 43:03doctors, kinda recognizing
• 43:05exactly how they work, what
• 43:07kind of class of drugs
• 43:09they are, when we determine
• 43:11using one versus another because
• 43:13there are differences when one
• 43:14is actually more potent,
• 43:16more effective, less toxic versus
• 43:18another. And then how we
• 43:20also think about sequencing therapies
• 43:22too to carry on what
• 43:23doctor Lina had spoken about.
• 43:25And so melanoma, you know,
• 43:27we stage melanomas to try
• 43:28to figure out what we
• 43:29need to do after the
• 43:30fact. Right? How do we
• 43:31keep it at bay? How
• 43:32do we prevent it from
• 43:33coming back?
• 43:34So for stage one melanomas,
• 43:36you know, the overall survival
• 43:38is pretty good.
• 43:40Ninety nine percent of five
• 43:42years, ninety eight percent of
• 43:43people are alive without having,
• 43:45succumb to their melanoma
• 43:47for early stage one a's.
• 43:49And you can see oftentimes
• 43:51as the stage increases, meaning
• 43:54stage two melanomas being thicker,
• 43:55stage three melanomas
• 43:57involving those lymph nodes, stage
• 43:59four melanomas become metastatic
• 44:01that unfortunately
• 44:02those survival outcomes do drop
• 44:05off.
• 44:06So how can we intervene?
• 44:09So again, upfront early stage
• 44:11melanomas, they go directly to
• 44:12my surgical colleagues, doctor Alina,
• 44:14doctor Westlake.
• 44:15They just get cut out,
• 44:17you know, hopefully,
• 44:19you know, we can figure
• 44:20out, we can get get
• 44:21control over that. There are
• 44:23specific nomograms that are actually
• 44:24publicly available. We just plug
• 44:26in the thickness,
• 44:28some risk factors associated with
• 44:30the pathology and figure out
• 44:31exactly what the risk is
• 44:33for that limp that melanoma
• 44:34to travel into the lymph
• 44:36node to then just make
• 44:37a very personalized decision
• 44:39about whether or not a
• 44:40lymph node biopsy is needed.
• 44:42Because we wanna we don't
• 44:43necessarily want to recommend more
• 44:45surgery. That's not gonna change
• 44:47the clinical outcome.
• 44:49Thicker melanomas,
• 44:50again, those get excisions
• 44:52plus or minus the sentinel
• 44:53lymph node biopsy.
• 44:55And then right now we're
• 44:56trying to figure out, okay,
• 44:58after that stage two melanoma
• 45:00comes out, do we offer
• 45:01additional treatments
• 45:03due to help minimize the
• 45:04risk of recurrence?
• 45:06For stage three melanoma, certainly,
• 45:08that was the the paradigm.
• 45:11Now as we're learning more
• 45:12about how to treat these
• 45:14upfront,
• 45:15maybe a little bit of
• 45:16systemic therapy followed by surgery
• 45:19to help minimize the long
• 45:20term need for any additional
• 45:21therapy would actually be beneficial.
• 45:23And then we'll also talk
• 45:25about stage four disease or
• 45:26basically distant metastatic
• 45:28disease. So, basically, the melanoma
• 45:30has now traveled to other
• 45:31sites in the body.
• 45:34So when we think about
• 45:35melanoma specific survival,
• 45:37again, we're thankfully
• 45:39not focused on those individuals
• 45:41who saw doctor Leventhal had
• 45:43their early stage melanoma that
• 45:45was very thick or sorry,
• 45:47very thin excised.
• 45:48We're kind of focusing on
• 45:50where we can move the
• 45:52field, where we can make
• 45:53changes to help improve patient
• 45:56outcomes
• 45:56long term.
• 45:58And so,
• 45:59yeah, past studies have shown
• 46:01sometimes earlier interventions, not waiting
• 46:04necessarily until the diseases come
• 46:05back, but actually prophylactically
• 46:08just starting some form of
• 46:09treatment
• 46:10for these higher risk melanomas
• 46:12may actually be beneficial in
• 46:14decreasing the risk for recurrence.
• 46:16And so it's always,
• 46:19counterbalanced
• 46:19by toxicity
• 46:21too. Everything that we prescribe
• 46:22has certain side effects.
• 46:24And so does that make
• 46:25sense to the individual in
• 46:27front of us? Do those
• 46:28side effects
• 46:29outweigh the potential benefits,
• 46:32verse,
• 46:33vice versa.
• 46:35And I'm sorry again, they're
• 46:36like Doctor. Levinthal, there's a
• 46:38little bit of a disconnect,
• 46:39when the slides were compiled
• 46:41here.
• 46:42When we, we also then
• 46:44do consider new adjuvant treatment
• 46:46because these drugs can work
• 46:47very well in the metastatic
• 46:49setting. We're trying to see
• 46:51if they can work even
• 46:52better in the stage three
• 46:54setting
• 46:55or even moving them up
• 46:56front, giving a little bit
• 46:57of treatment followed by
• 46:59surgery. And then deciding based
• 47:01on the pathology, whether or
• 47:03not additional treatment is needed.
• 47:05Now we always hark about
• 47:07tumor profiling and these more
• 47:09advanced melanomas. You know, we
• 47:11gotta wait for the tumor
• 47:12profiling to come back before
• 47:14we can make a treatment
• 47:15recommendation.
• 47:16That's because about in half
• 47:18of skin related UV exposed
• 47:20melanomas,
• 47:22people can have a BRAF
• 47:23mutation
• 47:24and that can be a
• 47:25game changer when we talk
• 47:26about adjuvant treatment or treatment
• 47:28after surgery to help minimize
• 47:29the risk of recurrence.
• 47:32BRAF mutations are unfortunately exclusive
• 47:35to NRAS mutations. So you
• 47:36have one or the other
• 47:37upfront.
• 47:38You know, sometimes we have
• 47:40individuals who
• 47:42develop,
• 47:43nodal metal melanoma,
• 47:45and we don't really know
• 47:46where the primary site is.
• 47:48So sometimes these mutations
• 47:50also help us to decipher
• 47:51where that melanoma originated from.
• 47:54Sometimes melanomas can regress automatically,
• 47:57with a with an,
• 47:59immune response upfront.
• 48:02Acral melanomas tend to have
• 48:03kit mutations.
• 48:05Mucosal melanomas can oftentimes have
• 48:07kit mutations, and then uveal
• 48:09melanoma is its own separate
• 48:10thing. It generally has a
• 48:12distinct,
• 48:13mutational profile unique to that.
• 48:17The other thing aside from
• 48:19tumor mutational status, that BRAF
• 48:21mutation
• 48:23is tumor mutational burden too.
• 48:25So as you can imagine
• 48:27over that chronic lifetime of
• 48:28unfortunate sun exposure,
• 48:31mutations
• 48:32add up and so that
• 48:33what that translates to is,
• 48:35the increase in number of
• 48:36mutations per megabase of DNA.
• 48:39The higher you have basically
• 48:42the more mutations that you
• 48:43have that can increase your
• 48:45chances of actually responding to
• 48:48immune therapy, it's a catch
• 48:49twenty two.
• 48:51This actually led to the
• 48:52first tumor agnostic approval for
• 48:55an anti cancer treatment.
• 48:57So this led to the
• 48:58approval of immune therapy, regardless
• 49:01of the cancer type. If
• 49:02you had a high enough
• 49:03tumor mutational burden,
• 49:05melanomas
• 49:06given that sun exposure is,
• 49:07has one of the highest
• 49:09mutational burdens.
• 49:12So immunotherapy,
• 49:14you know, we, we hear
• 49:15a lot about different types
• 49:16of immune therapy, but there's
• 49:18actually a number of different
• 49:19flavors of immune therapy.
• 49:21There's what we consider those
• 49:23immune checkpoint inhibitors, those monoclonal
• 49:26antibodies that we give Ivy
• 49:27every few weeks.
• 49:29There's also cytokine therapies,
• 49:31which is kind of the
• 49:32old version of immune therapy
• 49:34that's now resurfacing and having
• 49:36a renewed life in terms
• 49:38of the emerging clinical trials.
• 49:40There is now approvals
• 49:42in adopted cell transfer
• 49:44to so t cell based
• 49:46therapies,
• 49:46till therapies.
• 49:48There's cancer vaccines that are
• 49:50in clinical trials
• 49:52there's also oncolytic virus
• 49:54all of these different mechanisms
• 49:57basically help to augment your
• 49:59own body's ability to fight
• 50:01off the cancer
• 50:03So there was a dearth
• 50:05of
• 50:05systemic therapy options thirty years
• 50:08ago. It was chemotherapy
• 50:10and stage four melanomas
• 50:12were inevitably
• 50:13fatal.
• 50:15Since then though, thankfully with
• 50:17the advent of immune therapy,
• 50:18immune checkpoint inhibitors, we've had
• 50:20this resurgence
• 50:22of in our research interest
• 50:24in how do we
• 50:26utilize the immune system,
• 50:28leverage it to our advantage,
• 50:29to attack and directly destroy
• 50:31melanoma cells. So thankfully in
• 50:33the past fifteen years, we've
• 50:35seen a lot of new
• 50:36developments,
• 50:37drug developments, small molecule inhibitors,
• 50:40that will help to combat
• 50:42melanoma.
• 50:43So,
• 50:45you know, ongoing research as
• 50:46evidenced by the ellipsis here.
• 50:48So more to come,
• 50:49recently there's optula, which is
• 50:51combination anti PD one anti
• 50:54lag three there's to benefit
• 50:55us that got approved for
• 50:57uveal melanomas.
• 50:59And then finally,
• 51:00lip Aliso, which is till
• 51:02therapy.
• 51:04So, as I said, there's
• 51:05different treatment buckets and a
• 51:06lot of people come to
• 51:08me and say, oh, my
• 51:09insurance labeled the immune therapy
• 51:11as chemotherapy. I'm confused. What
• 51:13am I getting exactly?
• 51:15So chemotherapy,
• 51:16we talk about it only
• 51:18in the setting where
• 51:20all else fails, just because
• 51:21we know
• 51:23a lot of these treatments,
• 51:24carbotaxel,
• 51:25carbazine,
• 51:27temozolomide
• 51:28temodar
• 51:29really have limited efficacy
• 51:31they're not really seen as
• 51:32curative
• 51:33and so they're also toxic
• 51:35so we kind of reserve
• 51:36them kind of as a
• 51:38last resort it's really not
• 51:40a viable option
• 51:41Then we have targeted therapies.
• 51:43So it's targeted
• 51:45specifically towards a mutation.
• 51:47So this is very personalized
• 51:49medicine here. So if you
• 51:51have these mutations then potentially
• 51:54there
• 51:54is a pill that can
• 51:56target that mutation.
• 51:57So the most common one
• 51:58that we see in melanoma
• 52:00are B RAF mutations. So
• 52:01we have B RAF and
• 52:03MEC inhibitors targeting that again,
• 52:05there are kit inhibitors that
• 52:06are NTRK inhibitors that are
• 52:08Ross inhibitors as well.
• 52:10Then there's what we traditionally
• 52:12think of as immune therapy.
• 52:14So drugs like ipinivo,
• 52:16up dual lag, which is
• 52:18nivo rella,
• 52:19and then the single agent
• 52:20anti PD ones, nivo or
• 52:22Keytruda pembrolizumab,
• 52:24and then kind of our
• 52:25old standard,
• 52:26cytokine therapy. So like high
• 52:28dose IL two, for example.
• 52:30And then finally,
• 52:31The next advent is cell
• 52:33therapy. So this is till
• 52:34this is tumor infiltrating leukocyte
• 52:37therapy. It's where we actually
• 52:39harvest,
• 52:40tumor, grow out the t
• 52:41cells,
• 52:42and reinfuse them into patients.
• 52:45It's a one time treatment,
• 52:46but it is quite,
• 52:48an involved,
• 52:49process.
• 52:51So immune therapy back in
• 52:52the day when I was,
• 52:54a medical student, we were
• 52:56giving high dose IL two.
• 52:57That was kind of the
• 52:59standard treatment
• 53:00for metastatic melanoma.
• 53:03As you can see, the
• 53:04overall survival
• 53:06probability for these patients, it
• 53:08wasn't great. It was also
• 53:09really toxic, very difficult for
• 53:11patients to get through lots
• 53:13lots of issues with blood
• 53:14pressure support,
• 53:17edema, etcetera.
• 53:18So since then, kind of
• 53:20the central,
• 53:22study looking at immune therapy
• 53:25evaluated a combination of ipi
• 53:27and evo. And there's a
• 53:28central idea that the more
• 53:29different types of immune therapies
• 53:31you combine,
• 53:32the higher the response rate.
• 53:34The trade off is the
• 53:35higher the toxicity too.
• 53:36And so for every individual,
• 53:38we make a very personalized
• 53:40judgment call about what their
• 53:42ultimate goals are and tailor
• 53:44the treatment based on how
• 53:45much disease they have, where
• 53:47that diseases
• 53:48have, so that we can
• 53:49hopefully reap the benefits of
• 53:50potential response without too much
• 53:52added toxicity.
• 53:54And so again, this is
• 53:56where the field has moved
• 53:57in,
• 53:58and it's generated a revolution
• 53:59not only in melanoma treatment,
• 54:01but also has trickled down
• 54:02to other cancer types as
• 54:04well.
• 54:05So this is just a
• 54:06simple,
• 54:07table of the various systemic
• 54:09treatment options,
• 54:11you know, on the left
• 54:12there,
• 54:12immune therapy,
• 54:14as well as the response
• 54:15rates and their mechanisms
• 54:17of action,
• 54:18on the right targeted therapy.
• 54:20So these are your BRAF
• 54:21and MEC inhibitors,
• 54:23and you can say, Oh,
• 54:24wait a minute.
• 54:25The objective response rate, the
• 54:27chances of responding to these
• 54:29small molecule inhibitors is actually
• 54:31higher than immune therapy.
• 54:33Why are we recommending immune
• 54:34therapy as the upfront treatment
• 54:36for, metastatic melanoma?
• 54:38The issue is actually
• 54:40you get a much more
• 54:42durable response, meaning the chances
• 54:44of actual cure
• 54:46are much higher if we
• 54:48go with immune therapy
• 54:50the response rates are high
• 54:51yes there are potential
• 54:53permanent side effects
• 54:55like endocrine
• 54:56issues
• 54:57but
• 54:58the response
• 54:59can be long lasting.
• 55:00We can potentially actually cure
• 55:02people and put them into
• 55:04long term remission with immune
• 55:05therapy
• 55:06as opposed to targeted therapy.
• 55:09So that's why we favor
• 55:10immune therapy upfront, and this
• 55:12has been actually evaluated
• 55:13in a dream seek trial.
• 55:16And then also as a
• 55:17second line option
• 55:19t cell therapy lifolucil as
• 55:21well is available.
• 55:23Lifolucil,
• 55:25made the headlines just because
• 55:26it was the first
• 55:28t cell based therapy
• 55:30that was approved for a
• 55:31solid tumor
• 55:32and again it's not a
• 55:33walk in the park
• 55:35which is why we don't
• 55:36start with till therapy up
• 55:38front
• 55:39again there's a chance that
• 55:40we could potentially cure people
• 55:41with immune check point inhibitors,
• 55:43those in, systemic immune therapies.
• 55:45So we really reserve till
• 55:47therapy for those people who
• 55:48are refractory to prior treatments.
• 55:51So till therapy is quite
• 55:53involved.
• 55:55Patients have to undergo rigorous
• 55:56evaluation
• 55:57for cardiac function, pulmonary function.
• 56:00They have to have relatively
• 56:02slow growing tumor. They're not
• 56:04gonna blossom out of control
• 56:06within the next, two months
• 56:08because one, you have to
• 56:09get them to surgery. Doctor
• 56:11Alino has to remove those
• 56:13those tumors. We have to
• 56:14send it to the company.
• 56:15The company has to dissect
• 56:17the tumor out, make a
• 56:19single cell suspension, grow those
• 56:21t cells out, hit them
• 56:22with cytokines,
• 56:24basically make billions of copies
• 56:25of those T cells.
• 56:27Once those cells are ready,
• 56:28we have to get the
• 56:29patient back in, give them
• 56:30some low doses of chemotherapy
• 56:33to basically suppress
• 56:38t cells to come back
• 56:38in.
• 56:40Those t cells then get
• 56:41reinfused
• 56:42while the patient's in the
• 56:43hospital, and then they subsequently
• 56:45get low doses of IL
• 56:46two to help
• 56:48cells to survive now that
• 56:50they're back in you.
• 56:51So it's a quite a
• 56:53process. Patients have issues with
• 56:55low blood cell counts for
• 56:57the first month. They oftentimes
• 56:59need transfusion
• 57:00support.
• 57:01It is a very expensive
• 57:04treatment.
• 57:05It's a very costly in
• 57:07terms of time treatment, time
• 57:08commitment too.
• 57:10And so after that, then
• 57:12the patient gets discharged. They
• 57:13recover.
• 57:14And then it's kind of
• 57:15a waiting game to see
• 57:16if those T cells respond.
• 57:19Now immune checkpoint inhibitors. Whenever
• 57:22we counsel patients on, on
• 57:24potentially considering this treatment,
• 57:26again, it's not without side
• 57:28effects. So there are a
• 57:29lot of autoimmune
• 57:30related side effects that could
• 57:32incur,
• 57:33as as a result of
• 57:35immune checkpoint inhibitors. And, basically,
• 57:37it's bottom line is inflammation.
• 57:39It can happen anywhere. It
• 57:41can happen anytime
• 57:43so where that occurs
• 57:45kind of translates to the
• 57:46side effects so most common
• 57:47things are fatigue rash
• 57:50depending on the regimen
• 57:51sometimes diarrhea
• 57:53joint arthritis
• 57:55it can result in some,
• 57:57permanent side effects like type
• 57:59one diabetes,
• 58:01permanent loss of your thyroid
• 58:03function, pituitary
• 58:04adrenal function.
• 58:07Some things are we can
• 58:08replace with,
• 58:10medications like thyroid medications,
• 58:13low doses of steroids.
• 58:14Some a lot of these,
• 58:16side effects,
• 58:18are treatable, though. There are
• 58:20some very high risk side
• 58:21effects that we oftentimes have
• 58:23to counsel patients about
• 58:25because it can lead to
• 58:26lung inflammation, heart inflammation,
• 58:28inflammation of the nerves called
• 58:30myasthenia,
• 58:31gravis. And so,
• 58:33it is not without its
• 58:35risks.
• 58:36Now,
• 58:37you know, back in the
• 58:38day when these drugs were
• 58:39under clinical trial development, we
• 58:40were afraid to give it
• 58:42to people who had existing
• 58:43autoimmune issues.
• 58:45Thankfully, what we've discovered
• 58:47through the course of having
• 58:48these drugs available and trying
• 58:50to push the field to
• 58:51make them available for for
• 58:53more people is that a
• 58:55lot of these side effects,
• 58:56they don't necessarily
• 58:58flare in people who have
• 58:59autoimmune disease.
• 59:01Some things like PMR will,
• 59:03but other things like lupus,
• 59:05we can actually give these
• 59:07patients,
• 59:08with existing lupus, these immune
• 59:10checkpoint inhibitors.
• 59:11And oftentimes, we can we
• 59:13can get by, and they
• 59:14have a fantastic response.
• 59:16And so again it's not
• 59:18an absolute no that if
• 59:20you have an autoimmune disease
• 59:22that these therapies will not
• 59:24work for you or not
• 59:25safe for you.
• 59:26And so again this is
• 59:27where a clinical
• 59:29judgment
• 59:30kind of weighing the risk
• 59:31and benefits come into hand.
• 59:33So kind of just the
• 59:34lay of the land in
• 59:35terms of how we think
• 59:37about metastatic,
• 59:39melanoma treatment. So kind of
• 59:41up top on the far
• 59:42right here, you know, I
• 59:43kinda listed the drugs,
• 59:45in terms of efficacy.
• 59:47Again, the more efficacious, the
• 59:49potentially
• 59:50the higher the side effects.
• 59:51So we have ipinivo,
• 59:53that's kind of our tried
• 59:54and true regimen. If you
• 59:55have lots of disease,
• 59:57critical sites of disease, like
• 59:59brain metastases,
• 01:00:00That's one that we will
• 01:00:01oftentimes try upfront
• 01:00:03if we can think you
• 01:00:05can tolerate the side effects.
• 01:00:07Because, again, we don't wanna
• 01:00:08harm people,
• 01:00:10have a detriment to their
• 01:00:11quality of life with these
• 01:00:12treatments.
• 01:00:13Next is Zopdulilag.
• 01:00:15So people who have low
• 01:00:16volume disease will oftentimes try
• 01:00:18this first. And again, if
• 01:00:20there are side effects, we
• 01:00:21can deescalate
• 01:00:23to single agent Nivo or
• 01:00:25pembro.
• 01:00:26And if they don't have
• 01:00:27the response that we like,
• 01:00:28we can always escalate to
• 01:00:30ipinivo too.
• 01:00:31There's targeted therapies.
• 01:00:33And, again, there those come
• 01:00:35also in different flavors,
• 01:00:37and then cell therapy.
• 01:00:40So just a few,
• 01:00:41comments about some specific locations.
• 01:00:44So brain metastases.
• 01:00:46Doctor Kluger, you know, has
• 01:00:47a lot of clinical trials,
• 01:00:49a lot of investigation, and
• 01:00:50how do we improve responses
• 01:00:52for individuals with brain metastases.
• 01:00:55You know, melanoma,
• 01:00:56for whatever reason,
• 01:00:58probably from the neuroactogen
• 01:01:00merle origin of these cells,
• 01:01:02has a tendency to go
• 01:01:04to the brain.
• 01:01:06These lesions are not benign,
• 01:01:07obviously. They can bleed. They
• 01:01:09can cause seizures, they can
• 01:01:11cause edema, brain swelling,
• 01:01:13neurologic,
• 01:01:15loss of function.
• 01:01:16And so we actually do
• 01:01:18have better treatments now, more
• 01:01:19effective therapies that actually penetrate
• 01:01:22into the brain. We have
• 01:01:23radiation therapy that we can
• 01:01:25combine
• 01:01:26with these systemic therapies,
• 01:01:29but we still need ongoing
• 01:01:31research in radiation necrosis.
• 01:01:33That's where there's a lot
• 01:01:35of,
• 01:01:35cyclical inflammation in the brain
• 01:01:37that can lead to swelling
• 01:01:38too.
• 01:01:40You know, oftentimes,
• 01:01:41individuals ask me, okay.
• 01:01:44How do I know the
• 01:01:44treatment's working?
• 01:01:46We have to wait,
• 01:01:48you know, usually at least
• 01:01:50six weeks, if not three
• 01:01:51months, in order to figure
• 01:01:52this out.
• 01:01:53Because the issue is if
• 01:01:54we scan too soon,
• 01:01:56there is a phenomenon called
• 01:01:58pseudo progression.
• 01:01:59Those immune cells are activated
• 01:02:01from these systemic therapies.
• 01:02:02They can infiltrate into the
• 01:02:04tumor,
• 01:02:05cause a little bit of
• 01:02:06swelling, if you will, in
• 01:02:07that tumor whereby that tumor
• 01:02:09looks bigger on the scans,
• 01:02:10but it's actually because those
• 01:02:12immune cells are trying to
• 01:02:13get in there to do
• 01:02:14their job. And if you
• 01:02:15just wait a little bit
• 01:02:16longer, have a little patience,
• 01:02:18hopefully a little faith, and
• 01:02:20a few more prayers,
• 01:02:21then
• 01:02:22subsequently we see tumor shrinkage.
• 01:02:24And so that's why, unfortunately,
• 01:02:26we can't scan too soon.
• 01:02:27We have to,
• 01:02:29put our faith in these
• 01:02:30medications sometimes early on. And
• 01:02:32particularly if you're doing well,
• 01:02:34and symptoms are not any
• 01:02:35worse,
• 01:02:36oftentimes that's a sign of
• 01:02:38pseudo progression rather than true
• 01:02:40progression.
• 01:02:42Alright. So adjuvant treatment paradigms.
• 01:02:46So we talked about moving
• 01:02:48a lot of these effective,
• 01:02:50medications
• 01:02:51in the stage four setting
• 01:02:52early on to see if
• 01:02:53we can reduce recurrence risk.
• 01:02:56And so in stage three,
• 01:02:58you know, anti PD one
• 01:02:59drugs, so these are things
• 01:03:00like nivolumab,
• 01:03:02pembrolizumab,
• 01:03:03they do recur reduce recurrence
• 01:03:06risk by about fifty percent.
• 01:03:08However, they don't really improve
• 01:03:10survival.
• 01:03:11So what's our endgame? What's
• 01:03:12our target here? We need
• 01:03:14patients to live longer. We
• 01:03:15need them to do well
• 01:03:17longer.
• 01:03:18And so sometimes for for
• 01:03:20individuals, again, and this is
• 01:03:21where personal
• 01:03:22decision kind of priorities come
• 01:03:24into play. Maybe those side
• 01:03:26effects
• 01:03:26don't bode well if you're
• 01:03:28already kinda struggling and have
• 01:03:30other health issues.
• 01:03:31And so in those particular
• 01:03:33settings, if you do not
• 01:03:34have a BRAF mutation,
• 01:03:35sometimes a watch and wait
• 01:03:37approach,
• 01:03:38is actually makes more sense.
• 01:03:41If you do have a
• 01:03:41BRAF mutation,
• 01:03:43they these medications for stage
• 01:03:45three patients actually reduce recurrence
• 01:03:47risk by half, but they
• 01:03:48have also are starting to
• 01:03:50show improvements in survival too.
• 01:03:52So that's where waiting for
• 01:03:54that tumor mutational status to
• 01:03:56come back from the tumor
• 01:03:57resection
• 01:03:58actually does really impact how
• 01:04:00we think about treating individuals
• 01:04:02too. For stage two patients,
• 01:04:05anti PD one has been
• 01:04:06FDA approved, so nivolumab,
• 01:04:09pembrolizumab.
• 01:04:10However,
• 01:04:11the response, the benefit is
• 01:04:13a little bit less than
• 01:04:14stage three patients, and, again,
• 01:04:15there's no overall survival benefit.
• 01:04:20Alright. So neoadjuvant,
• 01:04:22I think doctor Alino has
• 01:04:23covered that very well, so
• 01:04:25we'll kinda skip over this.
• 01:04:28But really kind of, just
• 01:04:30and, again, just to kinda
• 01:04:31we we like to go
• 01:04:32over a case case reports.
• 01:04:35Okay?
• 01:04:36We're we're gonna pretend you
• 01:04:37guys are all medical trainees
• 01:04:39now that you've been you've
• 01:04:40lived the experience.
• 01:04:43So for example, let's think
• 01:04:44about, you know, a patient
• 01:04:45who had a right,
• 01:04:47abdomen melanoma.
• 01:04:49Stage three b,
• 01:04:51it was ulcer
• 01:04:53nonulcerated,
• 01:04:54but it had microsatellite.
• 01:04:55So there are little,
• 01:04:57areas of tumor
• 01:04:58adjacent to the primary site.
• 01:05:02BRAF,
• 01:05:03mutation status was positive, meaning
• 01:05:05the patient had a BRAF
• 01:05:06mutation.
• 01:05:08There was a clinically palpable
• 01:05:10lymph node, and so the
• 01:05:11decision was, as one of
• 01:05:13doctor Alina's paradigms,
• 01:05:15to treat with anti PD
• 01:05:16one therapy upfront.
• 01:05:18We gave two doses and
• 01:05:20actually the patient developed myocarditis,
• 01:05:22which is one of the
• 01:05:23most concerning side effects.
• 01:05:25And again, this kind of
• 01:05:26highlights that sometimes high risk
• 01:05:28sometimes comes with high reward
• 01:05:30too because what happened is
• 01:05:32that the tumor shrank.
• 01:05:35We did take a while
• 01:05:36for us to treat the
• 01:05:38myocarditis,
• 01:05:39get it under control to
• 01:05:40get the patient safely to
• 01:05:41surgery.
• 01:05:43However,
• 01:05:44so when that lymph node
• 01:05:45came out, there was still
• 01:05:46some viable melanoma. A lot
• 01:05:48of it was necrotic.
• 01:05:50The patient, because of that
• 01:05:52BRAF status, ended up getting
• 01:05:53an additional year of BRAF
• 01:05:54MEK inhibitors and remains disease
• 01:05:57free to this day. Myocarditis
• 01:05:59treated
• 01:06:00doing well.
• 01:06:02And so again, kind of
• 01:06:03leading into
• 01:06:04my colleague, Doctor. Ishizuka, who's
• 01:06:06gonna talk to you about
• 01:06:07about where the field is
• 01:06:08moving.
• 01:06:10We're gonna talk about where
• 01:06:12we can,
• 01:06:13move in terms of
• 01:06:15cancer vaccines,
• 01:06:16cytokine therapies,
• 01:06:18and adoptive cell therapies to
• 01:06:20try to push this forward.
• 01:06:22Thank you.
• 01:06:38Great. Well, thank you so
• 01:06:40much for the opportunity to
• 01:06:41be here today and to
• 01:06:42tell you a little bit
• 01:06:43about clinical trials here at
• 01:06:45Yale and Melanoma.
• 01:06:47So a couple of things
• 01:06:48I want to impart in
• 01:06:50the course of of our
• 01:06:51conversation tonight.
• 01:06:52One is just to know
• 01:06:54that that trials are are
• 01:06:56strong treatment options
• 01:06:57that going into the selection
• 01:06:59for a trial to be
• 01:07:00even considered at Yale, we
• 01:07:02meet together as a group.
• 01:07:04We discuss the merits. We
• 01:07:05make sure that there's a
• 01:07:06that we see a benefit
• 01:07:08for our patients to even
• 01:07:09put it on the roster
• 01:07:10of things we consider.
• 01:07:13That leads into number two,
• 01:07:15which is that
• 01:07:17whenever we suggest a clinical
• 01:07:19trial as a consideration,
• 01:07:20it's because we think that
• 01:07:22it is potentially,
• 01:07:24a thing that could offer
• 01:07:25offer benefit and the most
• 01:07:26benefit
• 01:07:27to our patients.
• 01:07:29The third thing is that
• 01:07:30our clinical trial portfolio
• 01:07:32is always evolving,
• 01:07:34that
• 01:07:35you know, I'll talk about
• 01:07:36some of the trials that
• 01:07:37are available tonight, but at
• 01:07:39any given day, I won't
• 01:07:40try and cover every single
• 01:07:41trial. And at any given
• 01:07:43day, that trial portfolio
• 01:07:45may continue to evolve. So
• 01:07:47it's always worth a conversation
• 01:07:48with us at any stage
• 01:07:50of care. Sometimes we have
• 01:07:51trials for earlier stage disease,
• 01:07:53sometimes for later stage disease.
• 01:07:55So it's always worth that
• 01:07:56conversation.
• 01:07:59Many of you will know
• 01:08:00this. Some of you will
• 01:08:01have participated in clinical trials,
• 01:08:02but clinical trials are are
• 01:08:04carefully designed studies. They're carefully
• 01:08:06designed treatments that start with
• 01:08:08a strong scientific rationale,
• 01:08:10usually
• 01:08:11years of of studies and
• 01:08:13and all sorts of experimental
• 01:08:14models,
• 01:08:16as well as kind of
• 01:08:17safety testing and and,
• 01:08:19you know, prior to ever
• 01:08:20becoming a clinical trial.
• 01:08:22There's a whole infrastructure of
• 01:08:24oversight for safety here at
• 01:08:26Yale and for the clinical
• 01:08:27trials that are run nationally.
• 01:08:31And that in many cases,
• 01:08:32clinical trials mean more frequent
• 01:08:34points of contact, right, for
• 01:08:36safety monitoring and so that
• 01:08:37we can observe,
• 01:08:38what's happening with the trial,
• 01:08:40in in you.
• 01:08:43Our fundamental motivation
• 01:08:45is twofold. Right?
• 01:08:47One thing is that we
• 01:08:48want to move the field
• 01:08:49forward.
• 01:08:50This is a group of
• 01:08:51people that go to bed
• 01:08:52thinking about these things. They
• 01:08:53get up thinking about these
• 01:08:54things.
• 01:08:55Every patient that we can't
• 01:08:57help stays with us. And
• 01:08:59so more than anything, we
• 01:09:00wanna put ourselves out of
• 01:09:01business. We wanna create new
• 01:09:02treatment options.
• 01:09:04And so there is a
• 01:09:05strong motivation to move the
• 01:09:06field forward scientifically.
• 01:09:08But the other thing we're
• 01:09:09looking for is to give
• 01:09:10the best options and give
• 01:09:11a greater array of options
• 01:09:12today.
• 01:09:14And so, you know, when
• 01:09:16we're thinking about trials, we're
• 01:09:17also doing that. We're thinking
• 01:09:18about how do we create
• 01:09:19a portfolio of options at
• 01:09:20as many stages of care
• 01:09:22as we can,
• 01:09:23and how do we pick
• 01:09:24the things and and look
• 01:09:26for the best opportunities
• 01:09:27that we think have, the
• 01:09:29greatest chance of benefit.
• 01:09:32So this is the guiding
• 01:09:34principle. What is best for
• 01:09:35the patient in front of
• 01:09:36me? Anytime we're having a
• 01:09:38trial conversation,
• 01:09:39that's what that's what we're
• 01:09:40thinking about. If we think
• 01:09:42that standard therapies are the
• 01:09:43best option for you, we
• 01:09:45will tell you in a
• 01:09:46very straightforward way.
• 01:09:49A question that sometimes comes
• 01:09:51up, people say, and I've
• 01:09:52heard my patients say to
• 01:09:53me, I don't wanna be
• 01:09:54a guinea pig. I don't
• 01:09:55wanna be I don't wanna
• 01:09:56be experimented on.
• 01:09:58And I think there's a
• 01:09:59couple things to think through
• 01:10:00in response to that question.
• 01:10:01Right? Some of them I've
• 01:10:03already kind of laid out
• 01:10:05that this trial never made
• 01:10:06it here unless we had
• 01:10:07thought it had a chance
• 01:10:08of benefit. And then fundamentally,
• 01:10:11we wouldn't be suggesting it
• 01:10:13if we didn't think it
• 01:10:14was as good or better
• 01:10:16than the standard of care
• 01:10:17options that we can offer
• 01:10:19at that time.
• 01:10:20And so, you know, there's
• 01:10:22a lot that goes into
• 01:10:23the process depending on the
• 01:10:24phase of the trial, but
• 01:10:25there's always a tremendous amount
• 01:10:27of of oversight,
• 01:10:29both within the clinic here
• 01:10:30and actually a whole staff
• 01:10:31of people outside of the
• 01:10:33clinic,
• 01:10:33many of which you get
• 01:10:34to know if you participate
• 01:10:36in, well, they'll come into
• 01:10:37the clinic as well in
• 01:10:38a clinical trial.
• 01:10:40So
• 01:10:41I wanna think through a
• 01:10:43couple of the the types
• 01:10:45of trials
• 01:10:46that are
• 01:10:47going on here at Yale
• 01:10:48now. I won't spend a
• 01:10:50long time on them. You
• 01:10:51could spend an hour talking
• 01:10:53about each of them, and
• 01:10:53I I think you guys
• 01:10:54wouldn't like that that much.
• 01:10:55But,
• 01:10:57you know, I'll talk about
• 01:10:58a couple of different lanes
• 01:10:59of of therapy.
• 01:11:00Right? A frontline study for,
• 01:11:03you know, if you haven't
• 01:11:04started treatment and actually some
• 01:11:06studies that are available
• 01:11:08even if if you've gone
• 01:11:09through and progressed through a
• 01:11:11prior treatment. Right? In some
• 01:11:13cases, while studies even earlier
• 01:11:14phase than these as well.
• 01:11:17And, you know, as a
• 01:11:18as a kind of framework
• 01:11:20for how we're thinking about
• 01:11:21this, doctor Tran laid out,
• 01:11:23as well as the targeted
• 01:11:24therapies, the great benefits that
• 01:11:26have come with the development
• 01:11:27of the immunotherapies.
• 01:11:28And so a lot of
• 01:11:29the things you'll hear me
• 01:11:30talk about, the ideas that
• 01:11:31are being tested in the
• 01:11:32clinic, focus on the, this,
• 01:11:34this general concept of how
• 01:11:36do we make the immune
• 01:11:37system work better against cancers.
• 01:11:39Right? You'll hear a lot
• 01:11:40of that.
• 01:11:41Okay.
• 01:11:42So
• 01:11:44just briefly,
• 01:11:45this is, the the first
• 01:11:47trial is one for patients
• 01:11:48who have not yet started
• 01:11:50therapy. It is a a
• 01:11:51frontline trial.
• 01:11:53It uses
• 01:11:54two agents, p d one
• 01:11:56and and LAG three that,
• 01:11:58doctor Tran described.
• 01:11:59In this case, it's testing
• 01:12:01a different type of PD
• 01:12:02one and LAG three, different
• 01:12:03types of drugs that target,
• 01:12:05at target these checkpoints
• 01:12:07and at different doses. And
• 01:12:09and, you know, part of,
• 01:12:10I guess, the learning there
• 01:12:11is it's it's potentially,
• 01:12:14we we do see, although
• 01:12:15many of these drugs target
• 01:12:17the same fundamental immune targets,
• 01:12:20that they can work in
• 01:12:20slightly different ways, that the
• 01:12:22the way you make the
• 01:12:23molecules, the way that you
• 01:12:25dose the molecules
• 01:12:26can have an effect on
• 01:12:27the overall immune response. And
• 01:12:29so, you know, the hypothesis
• 01:12:31here is that even though
• 01:12:32these two arms are targeting
• 01:12:34the same two sets of
• 01:12:35immune checkpoints,
• 01:12:37that,
• 01:12:37by using a different drug
• 01:12:39that is tuned differently and
• 01:12:40at different doses, that you
• 01:12:41may be able to get
• 01:12:42a better response.
• 01:12:45The the other trials I'll
• 01:12:47talk about are for later
• 01:12:48lines of care, so patients
• 01:12:50who have have progressed through
• 01:12:51some prior therapy.
• 01:12:53And, this is this is
• 01:12:54an oral medication
• 01:12:56called a PTPN
• 01:12:57two inhibitor. We won't quiz
• 01:12:59you on the the acronyms
• 01:13:00at the end.
• 01:13:02But the idea here is
• 01:13:03that you're doing a couple
• 01:13:04of separate things that are
• 01:13:06are different to improve the
• 01:13:07immune system. One is that
• 01:13:09you're helping,
• 01:13:10some of your immune active
• 01:13:12your active immune cells called
• 01:13:13t cells to function better.
• 01:13:15And the other is that
• 01:13:16you're targeting the tumors to
• 01:13:18become more responsive to some
• 01:13:20of the signals that are
• 01:13:21made by the t cells.
• 01:13:24Our our next trial that
• 01:13:26I'll mention
• 01:13:27is a way of doing
• 01:13:28two of the things that
• 01:13:29doctor Tran mentioned. She mentioned
• 01:13:31kind of cutting the brakes
• 01:13:32on the immune system with
• 01:13:33immune checkpoint inhibitors, but also
• 01:13:36kind of giving cytokines,
• 01:13:38that can sort of feed
• 01:13:40the the immune cells to
• 01:13:41help them grow and function.
• 01:13:43So in this trial, you're
• 01:13:44trying to combine those two
• 01:13:45ideas. And if you remember,
• 01:13:47doctor Tran mentioned that one
• 01:13:49of the problems with some
• 01:13:50of the cytokines is that
• 01:13:51they can have toxicities
• 01:13:53when given systemically, problems with
• 01:13:54blood pressure or other issues.
• 01:13:56And so in this case,
• 01:13:57you're trying to deliver
• 01:13:59this immune,
• 01:14:00cytokine just to the cells
• 01:14:02that need it. Right? And
• 01:14:03so that's that's one idea.
• 01:14:06Another variant of this idea
• 01:14:08that works along a similar
• 01:14:10line but using a different
• 01:14:11type of immune stimulatory
• 01:14:13signal is is this trial
• 01:14:14by Asher Bio using a,
• 01:14:17an agent that targets an
• 01:14:18immune cells called CD eight
• 01:14:20t cells and delivers to
• 01:14:22them this immune activating cytokine
• 01:14:24called IL twenty one.
• 01:14:26And so, you know, the
• 01:14:28idea here,
• 01:14:29it may work out to
• 01:14:30be that different patients will
• 01:14:31benefit from different things, and
• 01:14:33that's part of what we're
• 01:14:33trying to learn here as
• 01:14:34well.
• 01:14:37Finally,
• 01:14:39there's there's a trial that
• 01:14:40tries to take the to
• 01:14:42to try to tries to
• 01:14:43take out a negative,
• 01:14:46sponge that blocks an immune
• 01:14:48activating cytokine from working. So,
• 01:14:50again, this is an antibody
• 01:14:51therapy, but one that will
• 01:14:52actually,
• 01:14:53block the inhibitor.
• 01:14:55And a lot of the
• 01:14:56the fundamental science for for
• 01:14:57tumor immunology for this pathway
• 01:14:59was worked out here at
• 01:15:01Yale.
• 01:15:02But the hope is that
• 01:15:03this, this type of approach
• 01:15:06will take an important break
• 01:15:08off of the immune system
• 01:15:09and make it work better.
• 01:15:13You know, doctor Tran kind
• 01:15:15of weighed caught risks and
• 01:15:16benefits. You have to think
• 01:15:18about that with clinical trials
• 01:15:19as well.
• 01:15:21You know, in terms
• 01:15:22of cost, cost to to
• 01:15:24the patient,
• 01:15:25standard of care portions of
• 01:15:27the visit are generally covered
• 01:15:28by insurance, and then the
• 01:15:30study drug and study specific
• 01:15:31tests are usually paid for
• 01:15:33by the trial sponsor, but
• 01:15:35it doesn't mean that there
• 01:15:36cannot be any extra burden
• 01:15:38of travel and of time.
• 01:15:40In many cases, you're talking
• 01:15:42about further visits with us.
• 01:15:45And so that means, you
• 01:15:46know, getting you here to
• 01:15:47the clinic or at some
• 01:15:48in some cases, we can
• 01:15:50offer trials at our satellites
• 01:15:51sites as well. So it's
• 01:15:52not always here, but in
• 01:15:54many cases, the trials are
• 01:15:55centralized here.
• 01:15:57And then, of course, there's
• 01:15:58the time component.
• 01:16:00This added oversight for safety
• 01:16:02often means a a greater
• 01:16:04amount of time spent, you
• 01:16:05know, coming to clinic and
• 01:16:06and being with us in
• 01:16:07clinic.
• 01:16:10I just wanna leave you
• 01:16:11with, you know, the this
• 01:16:12idea again that,
• 01:16:15it's less about any particular
• 01:16:17trial that I I kind
• 01:16:18of talked very briefly about
• 01:16:19today and more about this
• 01:16:21overall framework,
• 01:16:22that,
• 01:16:23you know, these are are
• 01:16:25options that are reasonable to
• 01:16:26consider and that this is
• 01:16:27a conversation that we'd welcome
• 01:16:29having with with any of
• 01:16:31you or anyone,
• 01:16:32at any point.
• 01:16:34With that, I'll wrap up,
• 01:16:35and thank you.
• 01:16:43Have our our panels to
• 01:16:45come up to the front.
• 01:16:57But you guys have listened
• 01:16:58to us
• 01:16:59talk,
• 01:17:00And you haven't left yet,
• 01:17:01so that's always a good
• 01:17:02sign.
• 01:17:03But,
• 01:17:05you know, this is an
• 01:17:06opportunity we want all of
• 01:17:07you guys to
• 01:17:08ask us questions, anything that's
• 01:17:10come up during the talks,
• 01:17:12anything at all, and doctor
• 01:17:14Kluger will will moderate that.
• 01:17:16Excellent
• 01:17:17job. Yes. Let's do that,
• 01:17:19please. Let's start off with
• 01:17:20doctor Westwick, if you wouldn't
• 01:17:22mind. Thank you. Thank you.
• 01:17:25Yeah. I'm.
• 01:17:26I'm a plastic surgeon, and
• 01:17:28I work with the melanoma
• 01:17:29team together with doctor Alina.
• 01:17:32And Carlos, the PA who
• 01:17:33keeps me straight.
• 01:17:36Pretty much, you know, my
• 01:17:37job is
• 01:17:38to try to help
• 01:17:40any patient to get rid
• 01:17:41of their melanoma from a
• 01:17:42surgical standpoint.
• 01:17:44And being a plastic surgeon,
• 01:17:46when someone,
• 01:17:47including myself, makes a hole,
• 01:17:49I need to fix it.
• 01:17:50So that's my job.
• 01:17:54My name is Carla Becerra.
• 01:17:56I'm a surgical PA. I
• 01:17:57work with, doctor Westwick, doctor
• 01:17:59Lino, and doctor Khan sometimes
• 01:18:01as well.
• 01:18:03I've been a surgical PA
• 01:18:04here at Yale for almost
• 01:18:06nine years, and I've been
• 01:18:07in the melanoma field for
• 01:18:09thirteen.
• 01:18:11So I work with an
• 01:18:12incredible team, and I'm very
• 01:18:13happy to answer questions today.
• 01:18:16John Levinthal, we met earlier.
• 01:18:18Nice to see many familiar
• 01:18:19faces in the crowd.
• 01:18:22I'm Saj Khan. I'm one
• 01:18:23of the surgical oncologists. I'm
• 01:18:24fortunate to be doctor Aluno's
• 01:18:26partner,
• 01:18:27and I've been at Yale
• 01:18:28for about thirteen years now.
• 01:18:31Hi there. My name is
• 01:18:32David Schonfeld. I'm one of
• 01:18:33the medical oncologists here. So
• 01:18:35I I treat people with
• 01:18:36some of the the systemic
• 01:18:37therapies and clinical trials you
• 01:18:38just heard about, and I
• 01:18:39also see patients for follow-up
• 01:18:40and surveillance, and happy to
• 01:18:42take some questions.
• 01:18:45Thank you. So who's gonna
• 01:18:46brave it and ask a
• 01:18:47question?
• 01:18:48Anybody?
• 01:18:52Yes. Thank you. Doctor Tran's
• 01:18:54presentation, which was very interesting,
• 01:18:57and the the one slide
• 01:18:58in talking points around
• 01:19:01the current treatment paradigms,
• 01:19:05ipionivo,
• 01:19:05is that only a suggested
• 01:19:07course of action for stage
• 01:19:08four and not stage three
• 01:19:11patients now?
• 01:19:13Okay. I'm gonna let doctor
• 01:19:14I don't want to ask
• 01:19:14you. Take that one. So,
• 01:19:16so ipionivo is one of
• 01:19:18our standard
• 01:19:19go tos. You know, we
• 01:19:20we use it very commonly
• 01:19:21as Doctor. Tran mentioned for
• 01:19:23stage four patients.
• 01:19:24There's a couple flavors of
• 01:19:26giving it. We don't it's
• 01:19:28not the only option. There
• 01:19:29are other immunotherapies,
• 01:19:30especially another combo,
• 01:19:32that that
• 01:19:33comes with a little less
• 01:19:35efficacy, but a fewer side
• 01:19:37effects. So we we weigh
• 01:19:38always the, you know, the
• 01:19:39the patient's disease and and
• 01:19:40the specific,
• 01:19:41you know, medical history and
• 01:19:43other factors that go into
• 01:19:44it. But it is one
• 01:19:45of the more common one
• 01:19:45we use for stage four,
• 01:19:47and we are starting to
• 01:19:48use variations of it for
• 01:19:50earlier stage and and what
• 01:19:51doctor Tran and doctor Alino
• 01:19:53mentioned for what's called the
• 01:19:54neoadjuvant paradigm. So patients who
• 01:19:56need a little therapy before
• 01:19:58going to surgery, let's say
• 01:19:59because there's a palpable lymph
• 01:20:00node and we wanna give
• 01:20:01them something beforehand,
• 01:20:03doing a couple cycles of
• 01:20:05ipi nivo in a in
• 01:20:06a particular way way of
• 01:20:08dosing it is is one
• 01:20:09of the standard things we
• 01:20:10do now or or consider
• 01:20:11at least. But can I
• 01:20:13just add in there was
• 01:20:14a big trial where they
• 01:20:15compared they took state they
• 01:20:17took stage three melanomas out
• 01:20:19and then gave AP and
• 01:20:21Nivo, like, the two drugs
• 01:20:22versus the one drug, and,
• 01:20:23actually, there was a better
• 01:20:25outcome with one drug than
• 01:20:26with two?
• 01:20:27So it has been studied.
• 01:20:28It's just not beneficial.
• 01:20:31Good thing. So, I mean,
• 01:20:32I I'm a no longer
• 01:20:33surprised myself. So as a
• 01:20:34stage three patient,
• 01:20:36ipi and nivo is no
• 01:20:37longer a course of recommended
• 01:20:39action.
• 01:20:40Subjected. Stage three patients. That's
• 01:20:42been taken out. If it's
• 01:20:43already been taken out, yeah,
• 01:20:44we don't we don't generally
• 01:20:45use it there. But if
• 01:20:46it hasn't been taken out?
• 01:20:48Sometimes. Yeah. Yeah. It is
• 01:20:49a consideration. Yeah. If it's
• 01:20:51if if you're a stage
• 01:20:51three patient and there's some
• 01:20:53some disease we could feel,
• 01:20:56you know, it's something we
• 01:20:57would talk about and consider,
• 01:20:58yeah, for the right person.
• 01:20:59Yeah.
• 01:21:01Yes.
• 01:21:02Give us a brief definition
• 01:21:04of adjuvant and neoadjuvant.
• 01:21:07Okay. I'm gonna give that
• 01:21:09one to doctor Schonfeld again.
• 01:21:11Okay. I was gonna I
• 01:21:11was gonna hand it off
• 01:21:12to one of the surgeons.
• 01:21:13So so yeah. So,
• 01:21:15adjuvant,
• 01:21:16means after a more definitive
• 01:21:18thing, like a surgery typically.
• 01:21:20So adjuvant is after surgery,
• 01:21:22and then,
• 01:21:23neoadjuvant, and it can be
• 01:21:25any therapy. So adjuvant radiation,
• 01:21:26adjuvant systemic therapy, so an
• 01:21:28IV drug or a pill,
• 01:21:30And then neoadjuvant means before
• 01:21:31that more definitive therapy like
• 01:21:33a surgery. So that would
• 01:21:34be do that intervention like
• 01:21:36the, ipinivo, the immunotherapy
• 01:21:39first, and then go for
• 01:21:40the surgery. So it's either
• 01:21:42before or after the more
• 01:21:43definitive option, which is usually
• 01:21:45surgery.
• 01:21:46That's great feedback. Next time,
• 01:21:48we'll start with defining that.
• 01:21:50Okay. Thank you.
• 01:21:53Any other questions? I don't
• 01:21:55understand. What would be the
• 01:21:56surgery for a stage three
• 01:21:57patient
• 01:21:58with melanoma?
• 01:22:00Right.
• 01:22:01So so are you talking
• 01:22:02about specifically if they get
• 01:22:03what that that treatment beforehand
• 01:22:05and then they are you
• 01:22:06know, if you get the
• 01:22:07ipi nivo beforehand?
• 01:22:09If you're a stage three
• 01:22:10patient,
• 01:22:11what what would be a
• 01:22:12definition of a type of
• 01:22:13surgery that would be
• 01:22:15recommended?
• 01:22:16Maybe I'll hand that off
• 01:22:17to doctor Khan or doctor
• 01:22:18Westlake to
• 01:22:20And to be clear, sir,
• 01:22:21you're asking about lymph node
• 01:22:23positive disease.
• 01:22:24So,
• 01:22:25the surgery would generally be,
• 01:22:26you know, removing the primary
• 01:22:28tumor where it started from.
• 01:22:29So wide margin resection. So
• 01:22:30one centimeter for some tumors,
• 01:22:33two centimeters for additional tumors
• 01:22:34depending on the depth. And
• 01:22:36then, formal lymphadenectomy
• 01:22:37is what we'll often do,
• 01:22:39you know, particularly for axillary
• 01:22:41lymph node disease.
• 01:22:43You know, for,
• 01:22:44groin disease and pelvic diseases,
• 01:22:46things have changed and shifted
• 01:22:47a little bit, and there's
• 01:22:48less surgery that's being performed,
• 01:22:49but, an at lymphadenectomy.
• 01:22:52Which is sorry. Removing the
• 01:22:54lymph removing the lymph nodes
• 01:22:55from that basin. All of
• 01:22:56the lymph nodes.
• 01:22:58Yeah. We're probably becoming I'd
• 01:23:00love to see what doctor
• 01:23:00Alina says, but we're probably
• 01:23:02doing a little bit there
• 01:23:03was a time where we
• 01:23:04so there's different three levels
• 01:23:06of lymph nodes,
• 01:23:08level one, two, and three,
• 01:23:10and it's it's pretty aggressive.
• 01:23:12But,
• 01:23:13with immune therapy, we're probably
• 01:23:14not necessarily removing level three
• 01:23:16lymph nodes anymore. So,
• 01:23:18maybe let doctor Alino answer
• 01:23:19that. Yeah. So, you know,
• 01:23:22you can be in the
• 01:23:23same stage three bucket,
• 01:23:25and I can take out
• 01:23:26your melanoma.
• 01:23:28We do that sentinel node.
• 01:23:29We only find microscopic
• 01:23:30disease, and we learned that
• 01:23:32by taking out more lymph
• 01:23:33nodes, all we do is
• 01:23:35increase risk of swelling, and
• 01:23:36we actually don't make anybody
• 01:23:38live any longer. So in
• 01:23:40people who are still stage
• 01:23:41three, where you were diagnosed
• 01:23:43but it was microscopic, I
• 01:23:44told you I couldn't see
• 01:23:45it. The pathologist would have
• 01:23:46to tell us in a
• 01:23:47couple of days. You guys
• 01:23:48have heard my spiel. Okay?
• 01:23:50That's different than someone who
• 01:23:52comes into the clinic
• 01:23:54the first time that we
• 01:23:55meet
• 01:23:56them and we say,
• 01:23:58you have another spot, not
• 01:24:00just where the melanoma was.
• 01:24:01We feel something or something
• 01:24:03causes us to say, I'm
• 01:24:05really worried about your melanoma.
• 01:24:06Let's get a scan now.
• 01:24:08That's not microscopic
• 01:24:09disease anymore, and that's when
• 01:24:11we're talking about giving people
• 01:24:13some either an upfront therapy
• 01:24:15with a single or a
• 01:24:16double agent. Now that's very
• 01:24:18different than
• 01:24:19you come in.
• 01:24:21It's microscopic disease.
• 01:24:23We don't know if you'll
• 01:24:24be only
• 01:24:25the one in five person
• 01:24:27where you'll have more disease
• 01:24:28in the lymph nodes. That's
• 01:24:29why we don't take them
• 01:24:30all out. And that's when
• 01:24:32you meet with one of
• 01:24:33the colleagues, and they say,
• 01:24:34let's do the testing. You
• 01:24:36know? We don't have ev
• 01:24:37any evidence that there's any
• 01:24:38disease we can see on
• 01:24:39scans when we get the
• 01:24:40CAT scans or PET scans
• 01:24:42or the MRIs, and then
• 01:24:43we're we're trying to make
• 01:24:45that judgment.
• 01:24:46Do you need more? Are
• 01:24:47you gonna be the ones
• 01:24:48who are gonna be okay?
• 01:24:49And, again, that's one of
• 01:24:50the things that's really important
• 01:24:51that we all struggle with.
• 01:24:52Right? Because if we knew
• 01:24:53your melanoma was gonna come
• 01:24:54back, we'd have a different
• 01:24:56conversation.
• 01:24:56If we knew you're gonna
• 01:24:57have a toxicity,
• 01:24:59we'd have a different conversation.
• 01:25:00If we knew we could
• 01:25:01wait three years,
• 01:25:03then your melanoma would come
• 01:25:04back. You'd have three great
• 01:25:05years. You'd come and have
• 01:25:07to see us, but you
• 01:25:08know, and then it would
• 01:25:09come back, but you knew
• 01:25:10you had three good years
• 01:25:11where you didn't have to
• 01:25:12be exposed to any of
• 01:25:13the treatments. When every single
• 01:25:14one of you guys is
• 01:25:15coming in,
• 01:25:17and I encourage, you know,
• 01:25:18if if your doctors aren't
• 01:25:19speaking to you like that,
• 01:25:21that's when we're talking about.
• 01:25:22What are the pluses? What
• 01:25:23are the minuses?
• 01:25:25What are our theoretical risks?
• 01:25:27What are the fixed risks?
• 01:25:29And putting that all together.
• 01:25:31Right, that's what takes us
• 01:25:32an hour in the clinic.
• 01:25:33Right?
• 01:25:35That answer your question?
• 01:25:37Uh-uh. Not really. Yeah. Didn't
• 01:25:39it? Is a problem. Confused.
• 01:25:41I mean, if I have
• 01:25:41if it if if the
• 01:25:42melanomas reach my lymph nodes,
• 01:25:45is the course of action
• 01:25:46to take out all my
• 01:25:46lymph nodes or to put
• 01:25:48me on ipi or nebo?
• 01:25:50So should I I mean,
• 01:25:52to try to answer that.
• 01:25:53Okay. Yeah. So
• 01:25:54it first of all, things
• 01:25:56change
• 01:25:57over the period of our
• 01:25:58careers or the what the
• 01:26:00years that we've been doing
• 01:26:00that and more and more
• 01:26:01data become available. So what
• 01:26:03we did ten years ago
• 01:26:04is not what we did
• 01:26:04five years ago. What we
• 01:26:05do now is not exactly
• 01:26:06what we did five years
• 01:26:07ago either.
• 01:26:09So, you know, we have
• 01:26:10to take all of that
• 01:26:11into account. Now if the
• 01:26:13melon if the if there's
• 01:26:15nothing palpable,
• 01:26:17as doctor Lino says, if
• 01:26:18if this is microscope
• 01:26:32you start weighing the risks
• 01:26:33and the benefits. There is
• 01:26:34a ten percent or twenty
• 01:26:36percent depending on how big
• 01:26:37a person is and how
• 01:26:38many,
• 01:26:38and where where exactly the
• 01:26:40the lymph node basin is.
• 01:26:42But there's a risk for
• 01:26:43lymphedema
• 01:26:44long term.
• 01:26:45We always say, well, if
• 01:26:47we were going if the
• 01:26:48risk is high enough to
• 01:26:49justify giving adjuvant therapy that
• 01:26:51we just discussed, if we're
• 01:26:53going to give adjuvant therapy
• 01:26:54anyway, doing the surgery doesn't
• 01:26:56really add anything. So we
• 01:26:58may not go in and
• 01:26:59do the entire lymph node
• 01:27:00dissection. If we say we're
• 01:27:01not going in there to
• 01:27:03do adjuvant therapy for any
• 01:27:05reason, someone's got somebody's got
• 01:27:07an underlying disease, they we
• 01:27:08don't feel they can or
• 01:27:10should handle the immunotherapy,
• 01:27:12then maybe we would consider
• 01:27:13doing the nodal dissection. But
• 01:27:15what we know from at
• 01:27:16least three or maybe four
• 01:27:17surgical trials, correct me if
• 01:27:18I'm wrong, that in microscopic
• 01:27:21disease, just finding it in
• 01:27:22the central node and not
• 01:27:24doing a full nodal dissection,
• 01:27:25there's no difference in long
• 01:27:26term survival compared with monitoring
• 01:27:29it and if it does
• 01:27:30come back taking it out
• 01:27:31then.
• 01:27:32So
• 01:27:33early early lymph node dissection
• 01:27:35complete lymph node dissection versus
• 01:27:37late complete lymph node dissection
• 01:27:38does not impact survival.
• 01:27:40And particularly, if we're gonna
• 01:27:42be giving adjuvant therapy because
• 01:27:43then we're interfering with any
• 01:27:44potential cells that are there.
• 01:27:46Yeah. And if it's not
• 01:27:47microscopic I mean, I guess
• 01:27:48it sounds like the evolution
• 01:27:49is ipi and nivo is
• 01:27:50not a preferred path anymore.
• 01:27:53Ipi and nivo, we give
• 01:27:54if it's not microscopic and
• 01:27:56we can feel it Yep.
• 01:27:57And we don't wanna do
• 01:27:58a big surgery, we'll say,
• 01:27:59let's give a couple of
• 01:28:00cycles of ipi and nivo.
• 01:28:01No. That actually is what
• 01:28:02we've been doing in the
• 01:28:03last year. Okay. For stage
• 01:28:04three. For for big stage
• 01:28:06three, for bulky stage three
• 01:28:07that we can clearly feel
• 01:28:09and very high risk and
• 01:28:10a robust a robust patient.
• 01:28:13But we weren't doing that
• 01:28:14two or three years ago.
• 01:28:15That's a more recent development,
• 01:28:17the ipinivo.
• 01:28:19Taking it out and then
• 01:28:20doing epinevo, we don't do
• 01:28:21anymore. We tried, and it
• 01:28:22didn't didn't it didn't help.
• 01:28:24Yeah.
• 01:28:26Is that answer right now?
• 01:28:27That's a long answer. Okay.
• 01:28:29I'm happy to talk to
• 01:28:30you afterwards if you're like.
• 01:28:31Yeah. Go ahead. Yes. We
• 01:28:33have a question at the
• 01:28:34back there.
• 01:28:37Genius. And over the course
• 01:28:38of that period,
• 01:28:40the the the environment has
• 01:28:41really changed. Just watching this
• 01:28:43presentation
• 01:28:44was really amazing how much
• 01:28:45is happening.
• 01:28:47And my question as someone
• 01:28:49who's not in the medical
• 01:28:50scientific community, I read a
• 01:28:52lot of headlines.
• 01:28:54You know, the
• 01:28:55the current administration
• 01:28:57nationally that we're under is
• 01:28:58really cutting back funding in
• 01:29:01in research and science and
• 01:29:03cancer research specifically.
• 01:29:05Listening to Brandy talk about
• 01:29:07how amazing
• 01:29:09the hope and the the
• 01:29:10feeling of optimism she got
• 01:29:12coming here and being treated,
• 01:29:14I'm really curious.
• 01:29:15Thank you, Brandy.
• 01:29:17I'm really curious how what's
• 01:29:19happening in the political scene
• 01:29:21impacts the way you approach
• 01:29:23your job and and the
• 01:29:25research that's being done here,
• 01:29:26and if you're looking ahead
• 01:29:27and feeling hopeful.
• 01:29:30Yeah. So thank you for
• 01:29:31asking that question. That's a
• 01:29:32really charged one. And,
• 01:29:35if okay with everyone, I'm
• 01:29:36just gonna take a stab
• 01:29:37at answering it because you
• 01:29:39may you may get different
• 01:29:40answers from different people.
• 01:29:42We are worried. There's no
• 01:29:44question that we're worried about
• 01:29:45where the funding environment is
• 01:29:47going.
• 01:29:48We have had grants
• 01:29:50that were reviewed at the
• 01:29:51NIH that got top scores
• 01:29:53and and were not selected
• 01:29:55for funding
• 01:29:56in the last year for
• 01:29:57reasons that we we don't
• 01:29:59re they actually don't tell
• 01:30:00us, but things that wouldn't
• 01:30:01have happened two years ago
• 01:30:02or three years ago. However,
• 01:30:05with all of that, we
• 01:30:06have a really strong group
• 01:30:07here.
• 01:30:08And
• 01:30:10collectively, we actually still have
• 01:30:12a fair amount of funding,
• 01:30:13and we're very proud of
• 01:30:14that and grateful for that.
• 01:30:16Some of the funding comes
• 01:30:17from foundations like the MRA.
• 01:30:19We wanna thank them. The
• 01:30:20MRF is a different Melanoma
• 01:30:21Research Foundation, Melanoma Research Alliance.
• 01:30:24The Department of Defense has
• 01:30:26funded many of us, and,
• 01:30:27actually, doctor Ishizuka just got
• 01:30:29something from the NIH as
• 01:30:30well just a few weeks
• 01:30:31ago.
• 01:30:32So it we are we
• 01:30:34are seeing some funding coming
• 01:30:35in, and but we're still
• 01:30:36funded from older projects. So
• 01:30:38things that were submitted three
• 01:30:39years ago typically get funded
• 01:30:40for five years. We're still
• 01:30:41okay.
• 01:30:42The other beauty or advantage
• 01:30:44that we have here is
• 01:30:45that we work for Yale
• 01:30:46University,
• 01:30:47and we're very, very grateful,
• 01:30:50for that because there is
• 01:30:51a fair amount of of
• 01:30:53money within the system. And
• 01:30:54we have some,
• 01:30:55donors who've helped us a
• 01:30:57lot,
• 01:30:58in the last year. And
• 01:30:59now more than ever, we
• 01:31:00actually really are dependent on
• 01:31:02philanthropic
• 01:31:03donations.
• 01:31:04What we're hoping for is
• 01:31:05to ride out the wave
• 01:31:06until the NIH changes
• 01:31:09and things go back to
• 01:31:10where they are. But if
• 01:31:11anyone here wants to vote
• 01:31:13with their feet, please do
• 01:31:14so.
• 01:31:16We you know, but but
• 01:31:17the the the government does
• 01:31:19sometimes care about what people
• 01:31:20think. And the irony is
• 01:31:22that the sent the the
• 01:31:23house and the senate didn't
• 01:31:25actually cut the budget for
• 01:31:27NIH funding this year. They're
• 01:31:28just not dispersing the money.
• 01:31:29We don't know what they're
• 01:31:30doing with it, but it
• 01:31:31hasn't come into
• 01:31:33it hasn't come into this
• 01:31:34institution. So thank you so
• 01:31:35much for that question. I
• 01:31:36don't know if anyone wants
• 01:31:37to add to that. Maybe
• 01:31:38doctor Schonfeldt is someone who's
• 01:31:40also dependent on all of
• 01:31:41this.
• 01:31:42Thanks for including me.
• 01:31:45I don't know. No. I
• 01:31:47mean, I I I think
• 01:31:48you said it well, you
• 01:31:49know, doctor Kluger. I think
• 01:31:50it's concerning, and I think
• 01:31:51we're all worried because just
• 01:31:53the there's a lot about
• 01:31:54people to say the least.
• 01:31:55Yeah. I think that, you
• 01:31:55know, at least for the
• 01:31:56time being, things are very
• 01:31:57different than the way they
• 01:31:58used to be. And I
• 01:31:59think for the melanoma community,
• 01:32:01you know, there's still a
• 01:32:02lot to be done, but
• 01:32:03a lot of success. And
• 01:32:04we wanna continue on that
• 01:32:05track, and you can go
• 01:32:06even further and take it
• 01:32:07to the next level, and
• 01:32:08that's what we're all working
• 01:32:09on. So we're we're hopeful,
• 01:32:10and I think there's some
• 01:32:12many good things going on
• 01:32:13research wise. And funding wise,
• 01:32:15there's other sources like doctor
• 01:32:16Kluger mentioned between the foundations
• 01:32:18and philanthropy and still still
• 01:32:20some government funds, but I
• 01:32:21think we are worried and
• 01:32:22and just worried where things
• 01:32:23are heading overall. So
• 01:32:27Thank you for the question.
• 01:32:29Actual
• 01:32:30clinical trial?
• 01:32:34There are some
• 01:32:36so the neoadjuvant
• 01:32:37studies that doctor Olino talked
• 01:32:39about actually mostly came out
• 01:32:40of Australia and Europe.
• 01:32:43We do we do participate
• 01:32:45in them when we can.
• 01:32:47We may see more coming
• 01:32:48out of Europe because of,
• 01:32:50you know, because of funding
• 01:32:51cuts over here.
• 01:32:57Yes. Thank you.
• 01:32:59Slide on the four buckets
• 01:33:01for somebody who's not in
• 01:33:02the medical field. That was
• 01:33:03that helps kinda,
• 01:33:05separate the the, different,
• 01:33:07therapies.
• 01:33:09Did I understand right that
• 01:33:10you said, when you spoke
• 01:33:11about the immunotherapy
• 01:33:13that it has,
• 01:33:14more permanent response? It's more
• 01:33:16likely than that.
• 01:33:17And but yet more permanent
• 01:33:19side effects that would stay
• 01:33:21with could stay with the
• 01:33:22person.
• 01:33:23You know? I see. You
• 01:33:25know,
• 01:33:26diabetes
• 01:33:27and thyroid disease, etcetera, etcetera.
• 01:33:29So is that
• 01:33:31still of the four buckets,
• 01:33:32is that the number one
• 01:33:34place you go first? Or
• 01:33:36if you are BRAF positive,
• 01:33:38then you would go with
• 01:33:39targeted and then your secondary
• 01:33:41would be immune.
• 01:33:42So it was on doctor
• 01:33:44Chen's slide, the answer to
• 01:33:45your question. I'm gonna let
• 01:33:46her answer it though.
• 01:33:48Well, there was a lot
• 01:33:49there. We're not saying we're
• 01:33:50not having a standard.
• 01:33:53Wait. Wait. We we didn't
• 01:33:54cover this in clinic already?
• 01:33:58Just a few hours ago.
• 01:34:02So, really, it depends on
• 01:34:04the context.
• 01:34:05Right? If you have metastatic
• 01:34:07disease,
• 01:34:08then the chance of having
• 01:34:09a long term benefit and
• 01:34:11response
• 01:34:12and potentially even one day
• 01:34:14coming off of treatment entirely,
• 01:34:16if you have a complete
• 01:34:17response, meaning all the disease
• 01:34:19disappears on your scans, is
• 01:34:21higher with immune therapy.
• 01:34:23And so in those settings,
• 01:34:24sometimes a little risk outweighs
• 01:34:27or sorry. The
• 01:34:28the the benefits outweigh the
• 01:34:30risks in that scenario.
• 01:34:33With the targeted therapies, they
• 01:34:35work in the metastatic setting
• 01:34:38well for only so long,
• 01:34:40and then people relapse.
• 01:34:42It stops working. Resistance
• 01:34:44builds up, and then we
• 01:34:45start having to pivot again,
• 01:34:47talk about different therapies.
• 01:34:49When you're talking about stage
• 01:34:51three, though,
• 01:34:53they both have the same
• 01:34:54response
• 01:34:55in terms of decreasing
• 01:34:57relapse rates,
• 01:34:58but
• 01:34:59there is chance of a
• 01:35:01permanent side effect with the
• 01:35:03immune therapy that is not
• 01:35:05there with the targeted therapy.
• 01:35:07The targeted therapy also increases
• 01:35:10survival.
• 01:35:11So that's why in that
• 01:35:12stage three setting when we
• 01:35:14don't really know. Right? Are
• 01:35:16we doing you more harm
• 01:35:17or
• 01:35:18actually not providing any benefit
• 01:35:20with additional treatment? Technically, the
• 01:35:22tumor is out. The lymph
• 01:35:23nodes are out. There's no
• 01:35:25evidence of disease on the
• 01:35:26scans.
• 01:35:27And so to commit to
• 01:35:29something that could provide a
• 01:35:31permanent side effect,
• 01:35:33like type one diabetes,
• 01:35:35would be extremely detrimental because
• 01:35:37you maybe never needed that
• 01:35:38therapy at all.
• 01:35:40And so
• 01:35:41it depends on the stage.
• 01:35:43It depends on
• 01:35:45kind of personal decisions about
• 01:35:47the patient. This is why
• 01:35:48not everyone fits into the
• 01:35:50same mold. There's other variables.
• 01:35:52There's other lifestyle factors that
• 01:35:54we have to take into
• 01:35:55account
• 01:35:56to make sure that we
• 01:35:57personalize that decision and make
• 01:36:00the right decision
• 01:36:01as a group. You know,
• 01:36:02it's not what I recommend
• 01:36:04necessarily.
• 01:36:05It's what, like, the the
• 01:36:07where the values align in
• 01:36:09terms of improving long term
• 01:36:10patient outcomes
• 01:36:12and minimizing long term toxicity.
• 01:36:14Does that make
• 01:36:15sense? Okay.
• 01:36:18Okay. Necessarily, go for it
• 01:36:20first. Yeah. Just
• 01:36:22Thank you. So it's very
• 01:36:24interesting. In the past when
• 01:36:25we've had these symposia,
• 01:36:26all the questions were for
• 01:36:27the dermatologist,
• 01:36:30dermatologist, and he's just sitting
• 01:36:31there. So does anyone have
• 01:36:32a question for him going,
• 01:36:33going, going? Okay. Question is
• 01:36:35very good one. I mean,
• 01:36:35as in having had immunotherapy
• 01:36:38and the I
• 01:36:39personally haven't had any long
• 01:36:40term
• 01:36:41side effects. And not gonna
• 01:36:43move, but I think the
• 01:36:44cancer is out of me.
• 01:36:45And it was a lifesaver
• 01:36:46for me. But now it
• 01:36:47sounds like that's not as
• 01:36:49quick to be recommended course
• 01:36:50of action right now. Did
• 01:36:51I? And I is fascinating.
• 01:36:53One thing that was on
• 01:36:54doctor Tran's slide,
• 01:36:56and I think there was
• 01:36:57such an open question until
• 01:36:59four or five years ago
• 01:37:00for stage four, which is
• 01:37:02the same thing as metastatic
• 01:37:03disease, so a little different
• 01:37:04than than stage three, but
• 01:37:05whether one is better or
• 01:37:06not for these very issues.
• 01:37:07And so there was a
• 01:37:09specific trial that that doctor
• 01:37:10Tran mentioned that really
• 01:37:12was directly addressing that question
• 01:37:14in stage four patients, and
• 01:37:15there was such a wide
• 01:37:16gap in how patients did
• 01:37:18when they got immunotherapy first.
• 01:37:19So it really is what
• 01:37:21we go to if we
• 01:37:21can in in the stage
• 01:37:22four setting to where we
• 01:37:24think it really does make
• 01:37:25a difference if a patient
• 01:37:26can get immunotherapy.
• 01:37:27Yeah. And that trial was
• 01:37:29stopped early because they felt
• 01:37:30it was unethical to continue
• 01:37:32to give
• 01:37:33the targeted therapies first in
• 01:37:35stage four because the difference
• 01:37:36was so big.
• 01:37:41Any well, thank you all
• 01:37:43for coming. This was lovely
• 01:37:44and for the excellent questions.