Marco Davila, MD, PhD, posed a question to Joshua Richter, MD: with bispecific antibodies available off the shelf and without a manufacturing wait, what is the case for choosing chimeric antigen receptor (CAR) T-cell therapy instead, and is that decision clinical or operational? The pair discussed how sequencing CAR T-cell therapy before a bispecific antibody, rather than the reverse, may lead to better responses, and why the case for early cell therapy extends beyond a single treatment decision to a patient’s overall treatment journey.
Davila is physician–scientist and service chief of the Lymphoma–Myeloma Adoptive Cell Therapy Service at Roswell Park Comprehensive Cancer Center in Buffalo. Richter is associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and director of Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai.
Davila: I have a question for you, Josh. Bispecifics are off the shelf, repeatable, and available today without a manufacturing wait. In a patient who could get either therapy, either a T-cell engager or a cell therapy, what’s the case for giving CAR T-cell therapy instead? Is that decision clinical, or is it operational?
Richter: That’s a great question, and I’d say the billion-dollar question in myeloma is sequencing. The reality is, this is America: if a little is good, more is better, and much more is even better. In the myeloma world, it’s not that a patient gets CAR T or a bispecific. We have many patients who are going to get both. The question is, what’s better first: CAR T then bispecific, or bispecific then CAR T? So far, the data, much of which has come out of the University of Pennsylvania group, has shown that CAR T before a bispecific works better than the reverse sequence, with one of the biggest determinants of response to that second treatment being the time between attacks on BCMA. If you give a CAR T that attacks BCMA, you’re off therapy for months to years, and if you then come in with a bispecific, that distance between BCMA attacks is quite long. If you’re getting a BCMA bispecific every week, every other week, or even every month, and you progress and then come in for CAR T, that distance is going to be short. To me, you want to give patients not just the best therapy now, but consider the overall landscape of their treatment journey. To me, that’s the reason to give CAR T early on.
Davila: Very solid points. I am a cell-therapy clinician, so, you go to a surgeon, they’re going to recommend surgery. You go to a medical oncologist, they’re going to recommend chemotherapy. You go to a cell-therapy person, they’re going to recommend cell therapy. I believe the data strongly supports that as being a very good option for many patients, and earlier is better: you’re able to collect better T cells, get better production, and see lower toxicities. I want to be able to offer a therapy that can put patients in remission for years. The median response duration for some of these therapies hasn’t even been reached yet for patients treated in the second line, so I want to be able to offer that therapy to patients. I think of it a different way sometimes: rather than asking why I should give this therapy, I ask why I shouldn’t. There are some reasons that might exist, but I approach it from that angle. My goal is always to consider cell therapy strongly, and if there are logistical barriers, figure out how we can solve them. If there are clinical barriers, like a patient who has cardiomyopathy that raises concern about risk, can they see a cardiologist and get medical management that might improve their ejection fraction enough that I feel more comfortable with their risk? These are all things that come into play. I fall strongly within the cell-therapy camp.
