Secondary Malignancies After CAR T: How Big is the Risk?

Binod Dhakal, MD, MS, assistant professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, discusses the potential risk of secondary cancers like lymphoma and leukemia sometimes seen with chimeric antigen receptor (CAR) T-cell therapies, including ciltacabtagene autoleucel (cilta-cel; Carvykti).

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0:09 | There are case reports of the secondary T-cell lymphoma, and then some cases of secondary [acute myeloid leukemia (AML)] and [myelodysplastic syndrome (MDS)] reported with cilta-cel in trials, as well as with the other CAR T products. I think this is a risk that we cannot just ignore. We definitely have to be vigilant about it.

0:34 | Now, when we look at the overall risk, what is the overall risk in this setting, I think the data is still being followed, and we will know more as you go with the time. But I think that the data from CARTITUDE-4 [NCT04181827], and even the KarMMa-3 study [NCT03361748], which is a border, randomized study where they are comparing the CAR T with the standard of care, I think are gonna give more insights as we follow these patients because the number of cases of secondary malignancies, particularly the secondary MDS and AML seen in the CARTITUDE-1 patient population, is a little bit difficult to interpret the actual risk of this treatment because that is a single-arm study with no control arm and a heavily treated patient population. But I think the data from both CARTITUDE-4 and KarMMa-3, where this is being used in an early line that is less heavily pretreated than the CARTITUDE-1 [NCT03548207] patient population or KARMMA patient population, and with the control arm, I think once we follow these patients longer and see the cases of both MDS, AML, and also the secondary cancers, including T-cell lymphoma, this is going to give more insights on the actual risk of this treatment.

1:50 | Right now, I think, yes, it is a concern. We have to be vigilant about it, we have to educate the patients, we are aware of it. But in terms of offering the treatment to the patients, I would say that the benefits outweigh the risks, and it still has a better impact and better outcome for these patients.