All-Oral Therapy Improves Outcomes in AML Patients
Publication Title: All-Oral Treatment of Newly Diagnosed Acute Myeloid Leukemia
Summary
- Question
- This study examined the effectiveness and safety of an all-oral treatment regimen combining decitabine–cedazuridine, a hypomethylating agent, with venetoclax, a drug that targets cancer cells by inhibiting B-cell lymphoma 2 (BCL-2) proteins, for patients with newly diagnosed acute myeloid leukemia (AML) who were either 75 years or older or ineligible for intensive chemotherapy due to health conditions.
- Why it Matters
AML is a severe blood cancer often requiring intensive chemotherapy, which many older or medically compromised patients cannot tolerate. Current standard treatments for older patients involve combinations of oral pills with injectable drugs that can be burdensome for patients and caregivers. An effective total oral regimen would simplify treatment, improve accessibility, and potentially enhance quality of life while maintaining clinical efficacy. This research aims to address these challenges and offer a new option for this vulnerable patient group.
- Methods
- The researchers conducted a phase 1–2 trial across 34 centers in the United States, Canada, and Spain. A total of 189 participants with newly diagnosed AML were enrolled, divided into three trial phases. Participants received oral decitabine–cedazuridine for five days and oral venetoclax for up to 28 days per treatment cycle, with dose adjustments implemented in later trial phases to reduce side effects. The study assessed pharmacokinetics (how drugs are absorbed, distributed, and metabolized in the body), safety, and efficacy outcomes such as complete response rates.
- Key Findings
- The trial found no drug interactions between decitabine–cedazuridine and venetoclax. In the pivotal phase 2b, nearly half (47%) of patients achieved a complete response, and 63% had either a complete response or a partial response with incomplete recovery of blood cell counts. Median overall survival was 15.5 months. Common side effects included anemia (low red blood cell levels), neutropenia (low white blood cell levels), and febrile neutropenia (infection-related fever with low white blood cells), occurring in 25-30% of patients. Early adjustments to drug schedules reduced these side effects.
- Implications
- The study demonstrated that an all-oral regimen of decitabine–cedazuridine plus venetoclax is a viable treatment option for older or medically ineligible AML patients, offering comparable efficacy to injectable treatments while reducing logistical and quality-of-life burdens. These findings could reshape standard care practices, providing more accessible and patient-friendly treatment options.
- Next Steps
The authors suggest further research to confirm these findings in larger, randomized trials, and to study the addition of other novel or targeted agents to this double oral therapy backbone to further improve patient outcomes. Additionally, studies should explore the impact of this double oral regimen on patients' quality of life and healthcare resource utilization to better understand its broader benefits.
- Funding Information
- This research was supported by Taiho Oncology. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Yale University also provided funding and support for this research.
Full Citation
Authors
Amer Zeidan, MBBS, MD
First AuthorProfessor of Internal Medicine (Hematology)