CAR-T Meeting 2024 | CAR-T in multiple myeloma: progress in the space and what can be done to improve patient outcomes

Well, multiple myeloma is a complex disease and over the last years many novel compounds have been incorporated, resulting in a significant improvement in the overall survival. But as the treatment landscape is rapidly evolving, we realize the fact that after the first two or three lines of therapy, the majority of our myeloma patients are being exposed to the three main drug classes -proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. And we know that this population does represent an unmet medical need, because after PI, IMiDs, and anti-CD38, there is basically no standard of care, or I would say there was no standard of care. Now we have a new possibilities, new targets and new immunotherapy approaches.

During my presentation I discussed the role of BCMA CAR-T for relapsed/refractory myeloma. It is good to see how both ide-cel and cilta-cel showed to be effective in the triple-class refractory population. And these two BCMA CAR-Ts are indeed approved for this population. But the good information is these two BCMA CAR-Ts have already been evaluated in earlier lines of therapy, and we have Phase III clinical studies in which both ide-cel and cilta-cel showed to be superior to the control arms in patients with relapsed/refractory multiple myeloma after 2 to 4 prior lines of therapy for ide-cel and after 1 to 3 prior line of therapy for cilta-cel. So this is, I would say, the first point in order to improve the outcome for patients with multiple myeloma -to move the CAR-Ts earlier on. 

But we have learned other different situations that we can do in order to improve the outcome of patients with multiple myeloma. The selection of the patient -we have information coming from real-life studies showing how the selection of the patient is crucial.

And we have both data coming from the real-life study conducted with ide-cel, in which, for example, patients older than 70 showed to have an excellent outcome with ide-cel, because of the efficacy but especially because the toxicity profile is quite good.

In addition, another important point in which we can improve the outcome of patients with multiple myeloma throughout the CAR T-cell strategies is the bridging therapy because, once the T-lymphocytes are collected, trying to reduce the tumor burden as much as possible before proceeding to the lymphodepletion during the manufacturing time is crucial. In the KarMMa-3 clinical study, we had the opportunity to see how the bridging therapy was suboptimal for some patients and this resulted in the fact that a significant number of patients died because of progressive disease before they proceeded to the lymphodepletion.

So, this highlighted the need for optimal bridging therapies as, in KarMMa-3, we had the opportunity to see how patients in which, after bridging therapy, the disease responded or the disease was stabilized, the outcome was significantly better in comparison with those patients in which the disease progressed after the bridging therapy.

So in summary, I would say that there are different ways, with the information we have right now, to optimize the outcome of patients with multiple myeloma treated with CAR-T. And I would like to summarize saying that the selection of the patient is crucial, as well as the follow-up in the short and in the median time, and I would emphasize the role of bridging therapy in order to improve the outcome.