Joshua Richter, MD, asked Marco Davila, MD, PhD, to describe both sides of patient selection for CAR T-cell therapy: who represents the optimal candidate, and are there patients he would never refer for the treatment? The pair discussed how early referral for evaluation benefits nearly every patient with multiple myeloma, which comorbidities warrant real caution, and why the pool of patients considered CAR T-cell ineligible continues to shrink as clinical experience with the therapy grows.

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 is physician–scientist and service chief of the Lymphoma–Myeloma Adoptive Cell Therapy Service at Roswell Park Comprehensive Cancer Center.

TRANSCRIPT

Richter: You already alluded to it, that you go into this construct of give me a reason not to do CAR T-cell therapy. I’ll ask you both sides of the equation. [Who] in your mind is an optimal patient for CAR T? On the other hand, are there certain features where you’ll say, because of X, Y, or Z, I’m never going to do a CAR T in this patient?

Davila: First of all, who’s the optimal patient for referral? All of them. Maintenance, post maintenance, early biochemical relapse. I want to see them all. I may not recommend cell therapy for all of them, but I want to see them all. What describes optimal? To me, optimal means that they’re more than likely going to have a great response with minimal toxicity, and there the data is clear: as early as possible, second line, low tumor burden, minimal comorbidities. That’s the perfect picture. What is important to say is that’s not the only patient population that benefits. Patients who are older, who have comorbidities, who have higher tumor burden, they can benefit as well. There might be some more risk, there might be some more toxicities associated with it, but that doesn’t necessarily reduce their potential to be induced into long-term remission.

In terms of what I worry about, it’s patients who have significant neurologic disease, like they might already have parkinsonism or a seizure disorder. It can be hard for me to understand whether this patient is having neurotoxicity or whether this is their baseline disease. I get worried in those scenarios. Patients who have significant infections that are very hard to clear, or who frequently develop infections, I worry about those, because those are the patients where I always delay infusion. If a patient has an infection, I delay infusion, because the risk for toxicities is higher. If I see someone who’s having frequent infections, I worry about whether cell therapy is the best option for those patients. In patients who have a short life expectancy, say an 85-year-old patient with significant heart disease who is bed bound, I would still see that patient for referral, yes, but is this the best therapy to pursue, with collection, bridging, and hospitalization to manage all of that, given what fits with the patient’s goals? Probably not. I’d have the discussion with the patient, but there would probably be a scenario where I’d recommend against it.

Richter: Yeah, I completely agree. My views have changed since approval, and as our community globally improves its understanding of who, how, where, and when, there are relatively few patients I see who are not CAR T candidates. Even some of the ones with more comorbidities who are deciding between bispecifics and CAR T, to me that’s the conversation of, you won the lottery: do you want a lump sum, or do you want a monthly payment? The benefit of the lump sum is that I’m going to be with you during that initial phase, and you’re going to get immune recovery. I share your optimism that the percentage of people with relapsed myeloma who are CAR T ineligible is honestly shrinking.