David M. Dingli, MD, PhD, discusses the advantages and considerations of CAR T-cell therapy versus bispecific antibodies for relapsed/refractory multiple myeloma, helping patients make informed treatment decisions.
David M. Dingli, MD, PhD: It is difficult not to embrace these drugs as important therapeutic options for the patient with relapsed/refractory disease, and we have many of these patients because although many of our drugs work very well and for a considerable period of time, unfortunately patients progress, and when they progress, they become refractory to agents. Therefore, drugs with novel mechanisms of action become important, and that’s what the teclistamab, elranatamab, and talquetamab provide. I consider the bispecific antibodies as complementary to the chimeric antigen receptor [CAR] T-cell therapies that are available, and I want to emphasize the advantages and disadvantages of each because I believe that there are patients [for whom] a CAR T is appropriate and there are other patients [for whom] the bispecific antibodies would be the best choice.
To address the CAR T cells first, the advantage of the CAR T cells is that in principle the patient can receive a one-time therapy and can have a treatment-free period. For example, with Carvykti [ciltacabtagene autoleucel; Johnson & Johnson, Legend Biotech], median PFS [progression-free survival] now we have mature data of approximately 3 years. Let’s say the patient is fit, is motivated, has good social support, and we have a good treatment plan to keep the disease under control while the T cells are being manufactured. Then the patient, assuming they have no significant comorbidities or active infections, could be a very good candidate for chimeric antigen receptor T-cell therapy.
In contrast, you can have the 2 types of patients in my view where the CAR T may not be appropriate for them, at least in the short term. These are patients with rapidly progressive disease where therapy needs to be given immediately and, in that situation, an off-the-shelf therapy option becomes very attractive; and then also [there are] the patients whose comorbidities are such that they cannot potentially go to a CAR T-cell approach. If you allow me, I would consider some additional scenarios where the CAR T could be difficult. These will be, for example, the patient with poor social support, the patient [with] significant logistic problems with being away from home for considerable periods of time. That I suppose provides my view of CAR T vs the bispecific antibodies.
To address the next question with respect to, what would I choose for this patient? The patient has decided that they do not want the CAR T-cell therapy, or if we try to offer them a CAR T, we could not get a manufacturing slot. Then the logical next step is going to be a bispecific antibody. One could choose...teclistamab, or one can choose elranatamab, if we go with BCMA [B-cell maturation antigen], or one can think about the possibility of a GPRC5D bispecific, and we will go with talquetamab. Personally, in this situation, I would use a BCMA bispecific because we have more experience with this product that has been around for longer. As you know, teclistamab was approved last fall. We’ve gained quite a bit of experience with this agent. We know how it’s going to behave. We’ve learned how to handle potential toxicity both in the short term and in the longer term. Teclistamab would be my choice.
Suppose the patient would say, I do not want to completely eliminate the possibility that I could receive a CAR T cell in the future. If that was a possibility, then I would probably go with talquetamab, the reason being that I do not want to reduce the chances of a response to a CAR T later on if that was possible. We do know that at least if we treat a patient with one BCMA targeted agent and follow that with another BCMA targeted agent, the response rate goes down. Obviously I do not want to, at least in theory, jeopardize that type of response. I would treat the patients with talquetamab and leave the possibility of a BCMA CAR T open for the future, at least in theory.
Transcript is AI-generated and edited for readability.