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In today’s episode, we had the pleasure of speaking with Saurabh Dahiya, MD, FACP, and Shyam A. Patel, MD, PhD, about their research into the risk of developing second primary cancers (SPCs) following CAR T-cell therapy and how this risk, though low, may be mitigated. Dr Dahiya is an associate professor of medicine at Stanford University School of Medicine and Clinical Director of Cancer Cell Therapy in the Stanford BMT and Cell Therapy division in Palo Alto, California. Dr Patel is an associate professor in the Department of Medicine at the UMass Chan Medical School, as well as a hematologist/oncologist at UMass Memorial Medical Center in Worcester, Massachusetts.

In our exclusive interview, Drs Dahiya and Patel discussed the pathobiology of SPCs that develop after CAR T-cell therapy, potential SPC prevention strategies, and how SPC research may help optimize CAR T-cell product development in the future.

That’s all we have for today! Thank you for listening to this episode of 

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Podcasts

Drs Dahiya and Patel discuss how SPC research may help optimize CAR T-cell product development in the future.

How Second Primary Cancer Risk Factors Into CAR T-Cell Therapy Considerations: With Saurabh Dahiya, MD, FACP; and Shyam A. Patel, MD, PhD

Shyam A. Patel, MD, PhD, discusses the impact of donor-engrafted clonal hematopoiesis on the risk of disease relapse and survival outcomes with allo- and auto-HSCT.

Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT

Shyam A. Patel, MD, PhD, assistant professor, University of Massachusetts Chan Medical School, discusses the impact of donor-engrafted clonal hematopoiesis on the risk of disease relapse and survival outcomes with allogeneic and autologous hematopoietic stem cell transplant (allo-HSCT; auto-HSCT) in patients with hematologic malignancies.

Patel and colleagues conducted a comprehensive meta-analysis and meta-regression to evaluate the impact of donor-derived clonal hematopoiesis and pretransplant clonal hematopoesis on patient outcomes with allo-HSCT and auto-HSCT, respectively. The investigation evaluated 9 studies on auto-HSCT and 5 with allo-HSCT.

Results showed distinct effects of donor-derived clonal hematopoiesis on clinical outcomes depending on the type of transplant, Patel begins. For patients who underwent auto-HSCT, the pre-transplant clonal hematopoiesis was associated with poorer outcomes across several clinical parameters, including overall survival (OS), progression-free survival (PFS), and an increased risk of therapy-related neoplasms, he reports. These findings indicate that pre-transplant clonal hematopoiesis is a significant negative prognostic factor in auto-HSCT, potentially due to the superior engraftment potential of mutated hematopoietic stem cells compared to their wild-type counterparts, which may lead to worse overall outcomes, Patel explains.

In contrast, the impact of donor-derived clonal hematopoiesis in allo-HSCT showed a more nuanced effect, Patel continues. Although the presence of clonal hematopoiesis did not significantly affect OS, PFS, or non-relapse mortality, it was associated with a decreased risk of disease relapse, he details. This suggests a potential beneficial role of donor-derived clonal hematopoiesis in the context of allo-HSCT, possibly due to a graft-vs-leukemia (GvL) effect that may enhance the antitumor activity of the graft, Patelsays.

Overall, the study highlights a bimodal effect of clonal hematopoiesis, Patel states. Although it is predictive of inferior outcomes with auto-HSCT, it may provide some protective benefits with allo-HSCT, Patel notes. This distinction underscores the need for tailored approaches in screening for clonal hematopoiesis based on the type of stem cell transplant, he emphasizes. For auto-HSCT, prospective CHIP screening of the donor appears crucial due to its association with adverse outcomes with pre-transplant clonal hematopoesis, whereas the utility of such screening is less clear and may not be as critical for those undergoing allo-HSCT, Patelconcludes.

Shyam A. Patel, MD, PhD

Articles

How Second Primary Cancer Risk Factors Into CAR T-Cell Therapy Considerations: With Saurabh Dahiya, MD, FACP; and Shyam A. Patel, MD, PhD

Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT