CAR-T Meeting 2023 | Factors to predict the outcomes of patients with R/R myeloma treated with CAR-T therapy
In this video, Philippe Moreau, MD, Nantes University Hospital, Nantes, France, discusses risk factors for CAR-T therapy in relapsed/refractory (R/R) multiple myeloma. Prof. Moreau highlights several factors that may be integrated to predict patient response to CAR-T therapy, including presence of extramedullary disease, high-risk cytogenetics, tumor burden, and prior therapy. Prof. Moreau then goes on to discuss the importance of identifying the optimal sequencing of therapies in this patient population, and the added value of bispecific antibodies in the myeloma treatment armamentarium. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.
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Transcript (edited for clarity)
At this year’s meeting, in fact, I have discussed about risk factors for CAR-T cell therapy for patients with relapsed multiple myeloma. And what we know by now is that the dose of CAR-T matters, in fact. And when you are looking at the KarMMA study with ide-cel, if we are infusing an adequate number of CAR-T cells, 450 millions of CAR-Ts, the response rates are totally different, and the progression-free survival is also better as compared with lower doses...
At this year’s meeting, in fact, I have discussed about risk factors for CAR-T cell therapy for patients with relapsed multiple myeloma. And what we know by now is that the dose of CAR-T matters, in fact. And when you are looking at the KarMMA study with ide-cel, if we are infusing an adequate number of CAR-T cells, 450 millions of CAR-Ts, the response rates are totally different, and the progression-free survival is also better as compared with lower doses. We know that the expansion of CAR-T matters as well, and we may be able to predict those patients with a long response when there is a true in vivo expansion of the CAR-Ts. For example, with ide-cel, after 11 days, we have this peak of CAR-Ts, and when the peak is really high, the duration of response is also longer.
We know that some subgroups of patients are really benefiting less from CAR-T cell therapy. This is true for both CAR-Ts that are already approved, ide-cel and cilta-cel. We know that patients with extramedullary disease have lower response rates and also a shorter progression-free survival. This is also true for patients with a high tumor burden, ISS-3, and also patients with high-risk cytogenetics seem to benefit less, in fact, from CAR-T cell therapy.
We heard about an interesting presentation recently at ASCO and showing that we can put together different factors, such as tumor burden, the prior therapy that the patients did receive before the CAR-Ts, and we can integrate those different factors to try to evaluate the progression-free survival with four clusters, in fact. That’s not yet published, but that’s an indication of what we can do, in fact, to predict the outcome, and maybe to select, in fact, the best treatment option. Because we know that we have a restricted access to CAR-Ts currently, in Europe especially, we only have few slots for ide-cel, and in the majority of the countries, no access yet to cilta-cel.
And on the opposite, we have now teclistamab, that is the first bispecific antibody targeting BCMA that is approved, and with quite a lot of compassionate use programs all over Europe. Maybe we can try to select bispecific antibodies or CAR-T in the future, and that will be very, very important as well to understand what is the best sequence. And early data are showing that probably it is better to use, if available and if possible, CAR-T first, one and done, and bispecific antibodies at the time of the relapse.
If we are doing the opposite, if we are doing bispecific antibody first, then the CAR-Ts are less effective, in fact, and this is true for cilta-cel. And a recent paper from Dr Cohen showed that the response rate with cilta-cel after BCMA therapy, prior BCMA therapy, the response rate was decreased, in fact, from 95% to 60% only, and the PFS also was reduced, as compared with the PFS achieved in the CARTITUDE-1 study for the whole patient population. So that’s a very important question, the optimal sequence. And although the data are scarce and limited, in fact, we are thinking that it is better to use, if possible, CAR-T first, and bispecific at the time of progression of the disease.
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