CAR T Benefits in Cancer Outweigh Potential Risk of Secondary Malignancies

Matthew J. Frigault, MD, MS, clinical director of the cellular therapy program at Massachusetts General Hospital, discussed what a community oncologist should know about the ongoing FDA investigation of chimeric antigen receptor (CAR) T-cell therapies.

In November 2023, the FDA initiated an investigation looking into serious risks of T-cell malignancies in patients following treatment with CAR T-cell therapies.

Here, Frigault explains the benefits of CAR T-cell therapies for patients with cancer, highlighting that the single case report of a T-cell lymphoma in a patient who received a CAR T-cell therapy is not definitive evidence of CAR T causing the malignancy. While more research is needed, current data suggests CAR T-cell therapy is safe for most patients.

Transcription:

0:10 | I think the take home is that the clinical benefit of a CAR T-cell significantly outweighs any risk of a secondary malignancy. I think we sometimes forget that most of the chemotherapeutic agents that we give work by causing mutations in tumors. That is the mechanism of a lot of chemotherapeutics. When you're thinking about this in the CAR T standpoint, I think we really have a really microscopic lens on what's happening because this is a gene therapy, and CAR T cells are 1 of the very first gene therapies ever approved.

0:48 | [For] the single case report of a T-cell lymphoma in a patient who received cilta-cel [ciltacabtagene autoleucel; Carvykti] on CARTITUDE-4 [NCT04181827], really there's not a true smoking gun. I think this is a case where a patient had a preexisting cell that was potentially predisposed to become a lymphoma at some point, and that was actually in the manufactured product before the patient was even infused. That clone existed in that patient in advance, and then happened to be transduced with a CAR. I still haven't seen any data that was showing that the CAR was driving the lymphoma as opposed to say the other 3 mutations that were there in that tumor that were probably causative in terms of transformation. But again, we need to do more [research and get more] information. The take home is that these are still very safe therapies, 10s of 1000s of patients have received them, and I wouldn't worry too much just yet.