Dana-Farber physician-scientists presented results of more than 100 research studies at the 66th American Society of Hematology (ASH) annual meeting. Scientists shared findings across a range of hematologic disorders, underscoring the Institute’s dedication to innovation in hematologic oncology research, advances in early disease detection and intervention, and improving patient outcomes.
ASH is the world’s most comprehensive hematology event, attracting more than 20,000 specialists. This year’s meeting was held Dec. 7-10 in San Diego, Calif.
Two studies presented exciting advancements in the treatment of chronic lymphocytic leukemia (CLL):
- Jennifer Brown, MD, PhD, presented findings that a novel, fixed-duration drug combination — consisting of a second-generation BTK inhibitor, called acalabrutinib, plus a BCL-2 inhibitor (venetoclax), with or without a third blood cancer drug — shows deep and durable responses in patients with CLL. The findings stem from a planned interim analysis of a phase 3 international registration trial known as AMPLIFY, which included patients from 27 countries across North America, South America, Asia, Europe, and Oceania.
- Matthew Davids, MD, MMSC, presented findings that a time-limited regimen of acalabrutinib, venetoclax, and obinutuzumab (AVO), guided by measurable residual disease (MRD), showed positive results. The AVO triplet achieved high rates of durable response across a broad population of patients with CLL, and also demonstrated favorable outcomes for high-risk patients with TP53 aberrations. This is one of the first studies demonstrating the efficacy of time-limited triplet therapy in high-risk CLL.
A trio of studies yielded new insights into the treatment of acute myeloid leukemia (AML) for various high-risk subtypes:
- Shai Shimony, MD, presented findings from a genetic re-analysis of data from the pivotal phase 3 CPX-351 vs. 7+3 trial, which led to approval of CPX-351 for high-risk AML. The study revealed a survival benefit only for patients with AML-MR mutations. Patients treated with CPX-351 in the TP53, DDX41 and de novo groups had prolonged myelosuppression without improved disease-related outcomes, calling into question the role of CPX-351 in these patients.
- Jacqueline S. Garcia, MD, presented findings from a phase 1 trial that showed early efficacy of an all-oral maintenance regimen for high-risk MDS/AML patients after transplant. These patients are more likely to relapse after transplant. The investigators are encouraged by the safety, feasibility, and preliminary outcomes in this high-risk population.
- Richard M. Stone, MD, presented ten-year follow-up data from the RATIFY trial, which led to the approval of adding an agent called midostauren to chemotherapy for previously untreated adults with FLT3-mutant AML. In this ten-year follow-up, researchers found that the event free survival benefit of randomization to midostaurin vs placebo when added to chemotherapy was maintained over time, although the benefit for overall survival was diminished, likely due in part to aging.
Dana-Farber investigators also presented advances in systemic mastocytosis, a rare and heterogeneous condition that is often challenging for clinicians to accurately diagnose and treat:
- Daniel J. DeAngelo, MD, PhD, showcased the early efficacy of a novel drug, bezuclastinib, an inhibitor of KIT D816V. In all patients across all dose levels, significant responses were observed. Over 90% of patients achieved at least 50% reduction in mast cell burden as measured by laboratory and bone marrow tests.
- Virginia Volpe, MD, Shimony, and DeAngelo introduced a groundbreaking mathematical model based on recent clinical trial data. The model accurately distinguishes two key forms of systemic mastocytosis in over 90% of cases. These advancements could revolutionize diagnosis and treatment for patients facing this challenging condition.
Dana-Farber investigators presented three separate studies, all led by Irene Ghobrial, MD, with encouraging results related to the early detection and interception of multiple myeloma:
- Jean-Baptiste Alberge, PhD, presented a “Multiple Myeloma-like” (MM-like) score based on genomic markers that may help clinicians accurately predict if a patient with a precursor condition is at a high risk of their disease progressing to multiple myeloma. The tool could help clinicians identify patients that might benefit from an early intervention to prevent or delay progression.
- Sabine Allam, MD, presented findings that abnormal proteins called M-proteins in the blood, also called monoclonal gammopathies, may be present and detectable up to 22 years before a diagnosis of MGUS or multiple myeloma. The study reveals multiple myeloma’s earliest stages of disease development, enabling investigators to develop novel strategies for prevention, early detection, and interception of multiple myeloma.
- Floris Chabrun, PhD, PharmD, presented a tool called PANGEA 2.0 that improves stratification of patients with smoldering multiple myeloma based on their risk of progression to overt multiple myeloma. The model was created and validated using clinical data from 1,431 participants diagnosed with smoldering multiple myeloma at four international sites including Dana-Farber.
Dana-Farber researchers are also advancing efforts to develop evidence-based health equity interventions for children with cancer:
- Colleen A. Kelly, MD, presented findings from a pilot study of a program called Pediatric RISE (Resource Intervention to Support Equity) developed by pediatric oncologist and principal investigator Kira Bona, MD, MPH. The pilot study assessed the program’s feasibility and value to impoverished families with children being treated for cancer. The study successfully distributed the cash transfers to all the families either via direct deposit, pre-paid debit card, or online payment app. In addition, the families reported that they were very or somewhat satisfied with RISE and that they used the funds for rent/mortgage payments, groceries, utilities, and transportation and would recommend the program to other families. The pilot will continue in a larger, randomized, multisite phase 2 trial.
To learn more about these findings, please check out the highlights from the event.