Banerjee Discusses Emerging Research for CAR T in Multiple Myeloma

A multitude of studies on chimeric antigen receptor (CAR) T cell therapies were presented at the 2024 Transplantation and Cellular Therapy Tandem Meetings, several of which revolved around the use of CAR T in multiple myeloma. These included updates from the CARTITUDE-1 (NCT03548207) and CARTITUDE-2 (NCT04133636) studies investigating ciltacabtagene autoleucel (cilta-cel; Carvykti).

Rahul Banerjee, MD, assistant professor in the clinical research division at Fred Hutch, delved into the research from these studies presented at the meeting.

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0:05 | The other I think really interesting update was twofold. One was that there was a poster yesterday from Dr. Lim from Mayo Clinic and colleagues are the CARTITUDE-1 study. So ciltacabtagene autoleucel, which is a CAR T therapy in myeloma, the original US study of that product is now years out, 97 patients, and the median PFS we know is coming up on 3 years. Interestingly, they were able to really look at components of the CAR T infusion and very easily predict who is going to have a durable response and who wasn't. For example, how many effector CD8 cells or what we'll call killer T cells or cytotoxic T cells were in the bag vs CD4 cells vs for example, T reg cells or regulatory T cells. Those are cells that typically dampen the immune system and can also turn into CAR T regs, if that makes sense.

0:50 | And the more they had of those, the worse—Dr. Lim presented that poster yesterday, and she's the walking behind me right now. So the more of the CAR T cells, the CAR T regs that patients had, the worst they did. And that's really interesting. No one I think is at a position yet where we would try to prognosticate based on the composition of someone's bag, or try to triage our product to give someone based on someone's bag. But it was really interesting to say that, look, for patients where you know that based on the composition of T cells in CAR T, they're not going to do that, well, can we modify the T cells before they had a undergo collection or so forth? So that's 1 thing.

1:24 | The other interesting product also from the CARTITUDE series of trials was CARTITUDE-2 cohort B. That was an oral abstract yesterday, Dr. Helen Gaston and colleagues from Roswell Park, and they presented 2 cohorts. But the 1 that I think is most interesting is cohort B, is what we call functional high-risk myeloma. So these are patients where the myeloma comes back much earlier than expected, often a year after starting frontline therapy with with a transplant. Those are the patients who terrify me. They terrify all of us because they don't always have high-risk cytogenetics, meaning that we don't always know is this going to happen? This is a patient who they're in remission, they undergo transplant and all of a sudden, 3 months later, the myeloma is back well ahead of when it should, and that's really unfortunate. So I think here, they use cilta-cel in those particular patients CAR T and they found that the PFS in those patients, hard to say because we don't have enough follow up with at least 2 years, probably going to come up on 3 years similar to CARTITUDE-1.

2:13 | And that may suggest to us, and KARMMA has done something similar with ide-cel as well, that in these functional high-risk patients who have early relapse, unplanned relapse much earlier than planned, their prognosis directly has been terrible, nothing works for them, possibly CAR T may be the solution we're looking for to kind of just level the playing field. And whatever protoplasm, whatever mix of bad tumor biology and bad immune surveillance unfortunately leads a patient to have a relapse earlier than expected. CAR T may be our ticket to kind of get them out of that situation.