CAR-T Meeting 2024 | Overcoming challenges in CAR T-cell therapy for multiple myeloma

Immunotherapy is really the key and most exciting advance we’ve seen recently in the field of multiple myeloma, and this is about T-cell redirecting therapies. And in order to achieve this goal and harness the immune system and engineer or, I would say use, the T-cells to fight against myeloma. 

Today, the most popular ways are either cellular therapy using CAR T-cells or using the bispecific antibodies. And obviously, when it comes to bispecific antibodies, there is a variety of tumor antigens like BCMA, and some bispecific antibodies are already available, approved and widely used. You have also abispecific antibodies against GPRC5D, but also FcRH5.

When it comes to CAR T-cells, obviously there are so many constructs. Two of them are already approved ide-cel and cilta-cel. Of course, the most challenging part of the story, especially because today the largest experience is in the relapsed/refractory, highly advanced multiple myeloma population, is how to achieve long term progression-free survival. And it doesn’t look like in multiple myeloma, in contrast to non-Hodgkin lymphoma or acute lymphoblastic leukemia, that we are getting a sort of a plateau when using CAR T-cells for relapsed/refractory disease. 

Having said this, I think we need to acknowledge some subtle differences between the results with ide-cel, for instance, which is a different construct from cilta-cel. The result of cilta-cel, although it may not be easy to compare across trials, the results of cilta-cel are proving probably to be better in terms of outcome.

So clearly, today, when we look to the use of CAR T-cells in this relapsed/refractory disease landscape, the question is about how can we further improve on the current result? Is it by having or using a different T-cell population? Is it about the construct itself? Or is it about the tumor antigen or maybe we should use a dual targeting?

So there are plenty of exciting questions, but I believe that today, with the results we have with the two available constructs ide-cel and cilta-cel, this is proving to be extremely helpful to many patients with otherwise no available solutions. In addition, and I believe this is important and I would like to emphasize it, that one key benefit of using CAR T-cells in multiple myeloma is about the single-shot therapy and the treatment-free interval that will follow. And this is huge, tremendous in terms of quality of life and I’ve never met a single patient who didn’t like the treatment-free interval period.