Mark Hamilton, MD, PhD, on Analyzing PostCAR Myeloid Neoplasms

Commentary
Video

The hematology-oncology and BMT cell therapy fellow at Stanford University discussed implications of his institution’s findings on treatment-related secondary malignancies.

“One question that we're often asked is whether we should avoid therapy in patients with clonal hematopoiesis mutations, since they can be detected. We don't see any evidence, at least so far, that patients with lymphoma should be denied a life-saving therapy because they have the presence of these mutations prior to infusion. Of course, more work is certainly needed to better define and understand these processes, but as of right now, we find that they're kind of what we would expect.”

In early 2024, the FDA began requiring black box warnings for all chimeric antigen receptor T-cell (CAR-T) therapy products that had been approved by the agency at that time.1 The warnings were related to the potential risk for the development of secondary T-cell malignancies occurring in relation to treatment with BCMA- and CD19-directed genetically modified autologous CAR-T therapy.

In light of these warnings, interest has continued in gaining a better understanding a better understanding of these risks, including the mechanisms behind them and their similarity to other treatment-related risks in oncology. One such study on this topic was presented at at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California, by Mark Hamilton, MD, PhD, a hematology-oncology and bone marrow transplant (BMT) cell therapy fellow at Stanford University.2 The single-institution study evaluated data from a cohort of patients treated with CAR-T therapy for nonHodgkin lymphoma (NHL) at Stanford University.

In an interview with CGTLive® held shortly after the conference, Hamilton described the key results of the study and their implications. He pointed out that postCAR myeloid neoplasms seem to derive from preexisting clonal hematopoeisis and occur in patients with high treatment burdens that often have TP53 mutations. Hamilton also discussed some of the challenges and limitations of the study, and emphasized that more research on this topic is needed.

For more coverage of ASH 2024, click here.

REFERENCE
1. FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. April 18, 2024. Accessed February 5, 2025. News release. FDA. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed
2. Hamilton M, Phillips N, Lee D, et al. Single institution analysis of lymphoma treatment related post-CAR myeloid neoplasms. Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract #704
Recent Videos
Barry J Byrne, MD, PhD, the chief medical advisor of MDA and a physician-scientist at the University of Florida
Barry J Byrne, MD, PhD, the chief medical advisor of MDA and a physician-scientist at the University of Florida
Sarah Larson, MD, the medical director of the Immune Effector Cell Therapy Program in the Division of Hematology/Oncology at David Geffen School of Medicine at University of California, Los Angeles (UCLA)
David Porter, MD, the director of cell therapy and transplant at Penn Medicine
David Porter, MD, the director of cell therapy and transplant at Penn Medicine
Georg Schett, MD, vice president research and chair of internal medicine at the University of Erlangen – Nuremberg
Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado
Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado
Ben Samelson-Jones, MD, PhD, assistant professor pediatric hematology, Perelman School of Medicine, University of Pennsylvania and Associate Director, Clinical In Vivo Gene Therapy, Children’s Hospital of Philadelphia
Related Content
© 2025 MJH Life Sciences

All rights reserved.