Safety of CAR T-Cell Therapy Following FDA Warning on Risk of Secondary Malignancies Following Treatment

Sam Yamshon, MD, Weill Cornell Medicine, New York City, New York, discusses the safety and use of CAR T-cell therapy in clinical practice following the US Food and Drug Administration’s (FDA) warning in late 2023 regarding the risk of patients developing T-cell secondary malignancies following this treatment.

Transcript:

Dr Samuel Yamshon: Hi, I'm Sam Yamshon and I'm the director of Cellular Therapy at Weill Cornell Medicine in New York City.

Lymphoma Leukemia & Myeloma Network: In late 2023, the FDA released a warning regarding secondary malignancies of CAR T-cell therapy. Has this influenced the use of this therapy in practice?

Dr Samuel Yamshon: Late last year, the FDA did release a statement regarding secondary malignancies in CAR T-cell therapy and specifically T-cell malignancies.

Interestingly, this was a risk that was a hypothetical risk, even from the beginning of when we started using these therapies, because anytime you introduce new genetic material into T cells, there's a theoretical possibility of those T-cells becoming malignant.

In our experience, we didn't really see that borne out. When the FDA released this report, I think that it came somewhat as a surprise to many of us, and I think that as further data has come out, we've seen that the number of these T-cell malignancies that occur is quite small, that that risk is there, but it's numbering on dozens, out of the tens of thousands of patients that have received CAR T-cell therapy.

I think the piece that's critical is [that] CAR T-cell therapy is a potentially curative therapy for lymphoma, especially diffuse large B-cell lymphoma that [a patient] currently has. I think the risks of not giving this therapy for a disease that a patient currently has, because of a potential minute risk of malignancy that they could develop in the future, is probably not the best strategy moving forward.

At the Tandem meeting in San Antonio just a few weeks ago with CIBMTR and ASTCT, the FDA had a panel on this, and this question was asked. One thing that the FDA reiterated was they felt that the risks of developing these secondary malignancies from CAR T-cells were far, far outweighed by the benefits of receiving these therapies for hematologic malignancies.

I think the report has changed my practice [in that] I discuss this possibility more with patients, but I don't think that it's changed in how I deliver these therapies.