Liver transplant and beyond with David Mulligan

Transcript

• 00:16Welcome back, this session is being recorded.
• 00:21Hello, welcome to this session and
• 00:25it's my pleasure to to introduce
• 00:28Doctor David Milligan who is a
• 00:31professor of surgery and also
• 00:33Division Chair of Transplantation,
• 00:36Surgery and Immunology.
• 00:38So unfortunately he could
• 00:41not make it in person.
• 00:43So his talk is in his recorded so now
• 00:47the you know we'll play his regarding.
• 00:52I'm David Mulligan.
• 00:54I'm the chief of Transplant at Yale
• 00:57and I'm here to talk to you about
• 01:00transplantation for hepatocellular
• 01:01carcinoma and give you the UNOS optn update.
• 01:05As I'm in the immediate past,
• 01:07president of UNOS and the OPTN.
• 01:10So to overview,
• 01:12in case you're not familiar,
• 01:14the oversight and regulatory
• 01:16organization that overseas all of liver
• 01:18transplantation for the United States,
• 01:21which is the OPTN which
• 01:23is run by the company.
• 01:26The contractor of this federal contract
• 01:29UNOS to try and improve allocation and
• 01:33optimize transplantation for all patients
• 01:37in the United States and most recently.
• 01:41We've made a lot of changes in May of 2019,
• 01:45we implemented a national Liver Review
• 01:48Board in order to try to improve and
• 01:51standardize how we prioritize the
• 01:54patients who need exceptions scores to
• 01:57try to increase their access to life.
• 02:00Saving liver transplants
• 02:02when their meld score,
• 02:04which predicts their weightless mortality,
• 02:06doesn't serve them in an optimal
• 02:08way and how to fit these patients
• 02:10in in the right sequence.
• 02:12When they need a transplant in February,
• 02:15about five weeks before the pandemic
• 02:18of COVID-19 hit the United States,
• 02:21we implemented the acuity circles policy,
• 02:25which allowed us to improve
• 02:28access to life saving livers.
• 02:31Regardless of where a patient
• 02:33would live and reduce the disparity
• 02:35of those access to livers,
• 02:37I'll discuss with you in a few minutes
• 02:40how we then subsequently improved.
• 02:42And enhanced some of the guidelines and
• 02:45policies that were implemented with the
• 02:48National Liver Review Board back in October,
• 02:51August and September of 2020.
• 02:53And again this month this year to try to
• 02:56make further improvements and enhancements.
• 02:59As we implemented and utilized
• 03:01the National Liver Review Board
• 03:04and Acuity Circle allocations.
• 03:06What's coming around the corner is further
• 03:09enhancements to try to look at balancing.
• 03:12That's fair for patients who may be
• 03:16clustered around multiple transplant
• 03:18centers in a certain area with a
• 03:21certain acuity circle location and how
• 03:23to prioritize them in a more fair way.
• 03:27If they come from different
• 03:29transplant centers with the same
• 03:32underlying problem like HCC,
• 03:34but the donors are coming from
• 03:36different areas where they may be one
• 03:38or two points apart from one another.
• 03:40And we'll also talk about some.
• 03:43Of the latest enhancements that
• 03:45we've been discussing,
• 03:46looking at improving the alignment
• 03:49with the lyrae's classification of
• 03:51what HCC is and what would need a
• 03:55transplant and meet transplant criteria
• 03:57and what the OPT N classification is
• 03:59so that we have one common language.
• 04:02And then how we advantage patients
• 04:05who have had resections or even
• 04:07immunotherapy going forward into
• 04:10transplantation and prevent those
• 04:12patients from having disadvantages.
• 04:14So where are we right now?
• 04:16Patients who have HCC and cirrhosis
• 04:20and meet the standard criteria
• 04:22listed in OP TN policy are provided.
• 04:25The points on the MELD score
• 04:28system that are three points below
• 04:30the median meld at transplant,
• 04:33or what we popularly call MA t - 3
• 04:36and that is based on currently their
• 04:39transplant program and it's implemented.
• 04:43Those additional exception points.
• 04:45After a six month delay from onset
• 04:48of diagnosis and presentation to when
• 04:51they get those points and this was
• 04:54done after studies based on UCSF,
• 04:56where we saw that this was the optimal
• 04:59point where we could see the tumor
• 05:01biology for these patients and it was
• 05:03appropriate to implement them that high
• 05:06MELD exception score to get them access
• 05:09to transplant those standard criteria
• 05:12would include two HCC lesions that have.
• 05:16AFP's below 1000 or patients who were
• 05:19down staged to T2 from UCSF criteria and
• 05:23patients who had an alpha fetal protein
• 05:27less than 500 after treatment and a T2 HCC.
• 05:32Those are the standards they automatically
• 05:35would get implemented with their
• 05:37MA t - 3 anybody that's outside of
• 05:39those criteria would be referred to
• 05:41the National Liver Review Board,
• 05:43and again this is a panel.
• 05:45Of providers that are representatives
• 05:48from all the programs across the country
• 05:52not necessarily just in our local region,
• 05:55but the idea is there wouldn't be
• 05:58any local regional bias,
• 05:59and it would be the same standard guidelines
• 06:03that come from the guidance document.
• 06:06That was the that was actually
• 06:08developed by the OPTN and the Liver
• 06:11Intestinal Committee as well as the
• 06:13discussion from the NLRB reviewers.
• 06:16Now the NLRB was implemented in May of 2019,
• 06:20as I mentioned,
• 06:21and it replaced it.
• 06:23Replaced all the local regional review
• 06:26boards with one national system so that
• 06:29all exception cases could be reviewed
• 06:32and reviewed in a standardized way by
• 06:35members of the entire national consortium.
• 06:38This also allowed us to replace
• 06:42what we call the MELD elevator,
• 06:46which would.
• 06:46Increase a patient's exception scores by 10%.
• 06:49Mortality equivalents every three months
• 06:52that they did not receive a transplant
• 06:55so that a median meld at transplant
• 06:57where that patient was listed would be
• 07:01used as a criteria around which their
• 07:04access to transplant could be based.
• 07:07The meld?
• 07:07The meld elevator,
• 07:09therefore,
• 07:09would not continue to accrue where a
• 07:12patient who literally had a very low
• 07:15mortality on the list would then supersede.
• 07:17Patients who were going to die on the
• 07:20wait list with calculated MELD scores.
• 07:22The median melded transplant was calculated
• 07:26every six months from 365 day cohort,
• 07:31with most exception points on
• 07:33scores reupped every six months,
• 07:36and the goal of the NLRB is to reduce
• 07:38the relative priority of HC candidates
• 07:41and allocation that we're getting over
• 07:44prioritized by this meld elevator effect.
• 07:47And therefore HCC was getting
• 07:50too much priority acuity.
• 07:51Circle allocations came into place
• 07:53in February of 2020 and as I said,
• 07:56about five weeks before the onset
• 07:59of the COVID-19 pandemic,
• 08:01and this is important when you
• 08:03start to look at the results.
• 08:04This removed as designated by the
• 08:07Secretary of the Department of
• 08:10Health that we could no longer
• 08:12use donation service areas or our
• 08:15local areas for organ distribution.
• 08:17And allocation,
• 08:18and to more fairly allocate
• 08:20based on patients needs,
• 08:22regardless of where a patient
• 08:24would reside so that we
• 08:26could reduce the massive disparities
• 08:27that we saw in the Northeast and on the
• 08:30West Coast to be more equalized with the
• 08:33increase in in access to organs that
• 08:36we saw in the Southeast and central US.
• 08:39The areas that allocation would be made
• 08:42around would be the donor organ hospitals
• 08:45that were in concentric circles of
• 08:48100 and 52150 and 500 nautical miles.
• 08:51Around those hospitals and they
• 08:53would go and series of MELD scores
• 08:56and the impact on HCC by using these
• 09:00acuity circles was to try to optimize
• 09:03access for patients where they had a
• 09:06standard consistent level of access
• 09:09across the country and it changed the
• 09:12median meld of training at transplant
• 09:15calculation to try to be more equalized.
• 09:19So what are the enhancements?
• 09:21That we've seen to the NLRB since
• 09:24it's inception.
• 09:24Well, the first two enhancements that
• 09:26came out in August and September were
• 09:29to increase the ability for patients
• 09:31who needed a standard extension of
• 09:34their exception to be automatically
• 09:36approved if they met standard criteria.
• 09:38Secondly,
• 09:39that patients who had history of
• 09:42HCC that was more than two years
• 09:46prior to whatever treatment they
• 09:49received and the HCC recurred.
• 09:51Would be able to.
• 09:54Access their exception scores and
• 09:57they would therefore reapply for mild
• 10:01exceptions and could bypass the six week.
• 10:06The six month extension.
• 10:07The next three enhancements that have
• 10:10come more recently have to do with
• 10:12allowing patients who have received
• 10:14immunotherapy or who have had undergone
• 10:17a liver resection along with ablation
• 10:19therapies to be able to be instituted.
• 10:24There are mild exception score again without
• 10:27having to wait that six month waiting
• 10:29period and place them at the exception
• 10:32score when that recurrence was noted,
• 10:35as well as the chest,
• 10:38CT would only be required at
• 10:40the time of initial exception,
• 10:43but wouldn't be required every time
• 10:45an exception needed to be removed.
• 10:46So those are the most recent
• 10:48enhancements we've had.
• 10:49So after we've seen the implementation
• 10:51of the NLRB and these enhancements.
• 10:54We've seen a significant increase in
• 10:57the number of automatic approvals,
• 10:59which is decreased a lot of the workload
• 11:01of the National Liver Review Board.
• 11:03And as you can see on this graph over to
• 11:06the right hand side after implementation,
• 11:09people who are getting extensions
• 11:12after their first application,
• 11:1490% of them are getting automatic
• 11:16extensions because they meet the criteria
• 11:19and only about 10% need to go back to
• 11:22the NLRB for further review when the initial.
• 11:25Exception request come through about
• 11:27a third or automatic and about 2/3
• 11:31go through additional NLRB review.
• 11:34Now,
• 11:34what about this MATC around the
• 11:38donor hospital?
• 11:39It began as a problem was noted
• 11:43that in transplant centers,
• 11:45where a patient's MAT may be designated,
• 11:48for example, at 27,
• 11:50their MA T - 3 for an HCC patient,
• 11:54they might be in close proximity to
• 11:57another transplant center in an area,
• 11:59say for example New York,
• 12:01which is close to Philadelphia
• 12:03within a 250 nautical miles.
• 12:05Radius of a donor hospital and you
• 12:08can have the same patient in New York
• 12:11that might have an M at minus three
• 12:13of 28 and it's the same patient with
• 12:15the same diagnosis in Philadelphia,
• 12:17which would have an MA t - 3 of 27.
• 12:21Same patient, same diagnosis
• 12:23with two different MELD scores,
• 12:25and therefore it wasn't felt to
• 12:28be fair for those patients to
• 12:30be having the same diagnosis,
• 12:33but they were decreased in priority.
• 12:36To all the same patients at a
• 12:39different transplant center
• 12:40because they lived in New York,
• 12:41so the decision was made to calculate
• 12:45the MGMAT around each donor hospital
• 12:47for the groups of patients within
• 12:50that 250 nautical mile circle and use
• 12:53that as the criteria to reimplement.
• 12:56This is very extensive computer programming,
• 12:59as you can imagine,
• 13:01and in order to achieve this it's taken
• 13:04about a year since the problem was brought.
• 13:07Forward in the solution generated and
• 13:10therefore we'll see implementation
• 13:12later this year.
• 13:13Now where are we with the 18
• 13:16month monitoring reports for our
• 13:18acuity circle allocations?
• 13:20Well,
• 13:20if you look at 18 months prior to
• 13:23the development of the policy on
• 13:26February 3rd of 2020 and the post
• 13:29policy following that 18 months
• 13:31out to August of 2021,
• 13:34analysis based out on data that is
• 13:37recovered as of November 19th to 2021
• 13:40shows that as a result of the Acuity.
• 13:44Circle allocation and despite the
• 13:47problem with a worldwide pandemic,
• 13:50we are seeing a significant increase
• 13:54in wait list additions as well as wait
• 13:57list removals for death or two sick,
• 14:01significantly dropping increased number
• 14:03of deceased donor liver transplants,
• 14:07liver and other organ transplants like liver,
• 14:10kidney, liver,
• 14:10heart and a significant increase
• 14:12in the number of liver donors.
• 14:15Are covered, which is profound.
• 14:17We've seen when you look at the
• 14:20cumulative in the incidents of
• 14:22transplant for liver wait list additions,
• 14:25Meld, Peld score by status or era,
• 14:28that in every case status 1A and 1B.
• 14:32The high MELD patients by three MELD
• 14:36points on declination that there is
• 14:40a significant increase in the post.
• 14:44Implementation of equity.
• 14:46Circles and access of patients for
• 14:50transplant all the way down to melds of 15.
• 14:54When you look at the removal
• 14:56for death or too sick,
• 14:57the patients who have been in
• 15:00the post acuity circle allocation
• 15:02era are significantly advanced.
• 15:05At every MELD score,
• 15:07especially in the higher MELD
• 15:09scores from MELD 29 and up.
• 15:10When you look at the ceased
• 15:14donor liver alone transplants.
• 15:16My meld score and status.
• 15:18You can see that the utilization of
• 15:22donation after circulatory death is
• 15:24significantly greater in patients in the
• 15:27post era of the melds between 15 and 28,
• 15:31so that we've been able to optimize
• 15:33the utilization of these DCD donors
• 15:35and increase the total number of
• 15:37transplants we've been able to perform.
• 15:39And similarly,
• 15:40when you look at this graphic,
• 15:42you can see that one of the complaints
• 15:44about having to ship livers.
• 15:46Greater distances did flatten
• 15:48out to some degree with
• 15:51with increasing distances across
• 15:55the larger nautical mile distance.
• 15:58But as you can see, the amount of
• 16:01increase has actually been relatively
• 16:04small compared to what the concern was.
• 16:07And if you see the coldest chemia time,
• 16:10even with a somewhat increased
• 16:12distance and shipping,
• 16:13the coldest chemia time was able to
• 16:16stay less than six hours on the average.
• 16:19Finally, when we looked at the rate of
• 16:22the discards or the livers recovered
• 16:24and not used in almost every case
• 16:27post acuity circle except in region 5,
• 16:30region 8 and region nine,
• 16:34we can see that post acuity circle
• 16:38allocation the discard rates
• 16:40were lower and the new era.
• 16:42Now one year post transplant patient
• 16:45survivals for deceased donor liver
• 16:48alone by era was significantly better
• 16:51in patients that were transplanted
• 16:53in the post acuity circle era,
• 16:56which is exactly what we were hoping to do,
• 16:59reduce disparity,
• 17:00increase access to transplants,
• 17:02increase transplants,
• 17:03and increase and decrease death
• 17:05rates on the wait list.
• 17:08And this is what we saw so specifically
• 17:10for HCC patients with exceptions for HCC.
• 17:14Did not really see a change in
• 17:16deaths on the wait list and they did
• 17:18not really also see an increase in
• 17:20transplants that much so it didn't have
• 17:22a major effect on the HCC patients.
• 17:25We did see a slightly lower incidence
• 17:29of patients transplanted for HCC
• 17:31which also was probably the right
• 17:34thing to do and we did see that
• 17:37the mean MELD score or PELD score
• 17:40for patients with HCC decreased
• 17:42from a meld of 28 to a meld of 26.
• 17:45And this resulted in a shift of
• 17:48patients in the post acuity circle era
• 17:52to being transplanted for HCC and a
• 17:56meld in the 15 to 28 era area versus
• 18:00the higher melds where that meld
• 18:03elevator where transplanting patients
• 18:05with HCC even out to melds of 40 in the past.
• 18:10When we see the look to the future
• 18:12to find out what's coming up next,
• 18:15as we said,
• 18:16there's going to be more alignment,
• 18:18and in the terminology between
• 18:20the lyrae's classification for HCC
• 18:22along with the OPT N classification.
• 18:25So there'll be one common terminology.
• 18:27We will see patients that have
• 18:30further refinement for HCC that
• 18:32recurs in patients regardless of
• 18:35whether they've been treated with
• 18:38resection ablation embolization.
• 18:40Or immunotherapy and bypassing the
• 18:42six month wait and moving forward.
• 18:45We'll be discussing the concept
• 18:48of continuous distribution,
• 18:49so we'll get away with arbitrary
• 18:51circle allocation and move toward
• 18:53a classification system in which
• 18:55we'll be looking at a point based
• 18:58system where patients with ACC will
• 19:00be getting points based on their
• 19:02need for a transplant different than
• 19:04their mortality on the wait list.
• 19:06And so this will be a project
• 19:08that's oncoming.
• 19:09I want to thank you for
• 19:10the ability to present.
• 19:11This information to you and we'll look
• 19:14forward to answering your questions
• 19:15in the upcoming discussion session.
• 19:18Thank you.