CAR-T Meeting 2023 | CAR-T therapy in multiple myeloma: recent updates, clinical trials and future outlooks

Multiple myeloma is another indication for CAR-T cells. We are very fortunate today having two constructs being approved in relapsed/refractory multiple myeloma, namely, ide-cel and cilta-cel. Both constructs are targeting BCMA, the B-cell maturation antigen. These CAR-T cells in myeloma are really providing a big hope for many patients who are in need. Clearly, there is no doubt about the role of these CAR-T cells in the management of relapsed/refractory multiple myeloma, especially those patients who received and relapsed after receiving the IMiDs, the proteasome inhibitors, and the anti-CD38 monoclonal antibodies, the so-called, for instance, penta-refractory patients.

Obviously, in contrast, for instance, to DLBCL lymphoma, it doesn’t look like that there is a plateau in this disease setting in multiple myeloma because patients continue to relapse over time. There may be subtle differences between ide-cel and cilta-cel, we need a little bit more follow-up to make sure that the results are confirmed over the long term. However, it is important to notice that… and this happened just a few hours ago: that we have a randomized Phase III trial, namely the KarMMa-3 trial, showing the superiority of using CAR-T cells in earlier lines of relapse versus the best available therapy options.

This is really a turning point. It’s not only about the KarMMa-3 trial, which has just been published in the New England Journal of Medicine. We have also a press release recently about the CARTITUDE-4 trial. Obviously, it’s only a press release, but, definitely, the trial also met its primary endpoint showing the superiority of the CAR-T cells in multiple myeloma.

The field is moving rapidly. Probably, we’re going to be using these CAR-T cells earlier in the course of the disease and maybe in a couple of years… Three/four years, I don’t know, we will get also the results in frontline therapy because we have trials now ongoing in the elderly population against standard of care but also randomized trials against autologous stem cell transplantation.

You can appreciate that CAR-T cells in multiple myeloma are here to stay. Of course, I’m not minimizing the role of the other major immunotherapy tool, namely the bispecific antibodies, T-cell engagers, which are also leading to some very, very exciting results. It’s not only about BCMA being a target for CAR-T cells or for the bispecific antibodies. But now, we have constructs of CAR-T cells but also bispecific antibodies targeting other tumor antigens, like GPRC5D, both for CAR-T cell and bispecifics. But we have also, in bispecific, the FcRH5. This field is incredibly moving fast, and I think the treatment landscape will change. The whole algorithm of the management of the patients will be modified in the near future. This is always great news because, at the end of the day, it’s about improving the outcome of these patients and increasing the proportion of the patients who will live long and well, and that is the goal.