EBMT 2026 | Approaching the sequencing of bispecific antibodies and CAR-T in multiple myeloma

In multiple myeloma, we’ve seen quite incredible advances over the last couple of years. And all of this is about the advent of T-cell engagers, the immune therapies, whether CAR T-cells, the anti-BCMA CAR T-cells, or the bispecific antibodies. BCMA is the most widely tested and used target when it comes to CAR T-cells, with ide-cel and cilta-cel, both of them are approved. When it comes to bispecifics, we have teclistamab, elranatamab, and linvoseltamab. And, of course, now we have accumulated data and evidence showing, for instance, that cilta-cel can be used in early relapse, thanks to the CARTITUDE-4 randomized trial showing a clear PFS, progression-free survival, but also overall survival advantage in favor of the use of CAR T-cells. On the other hand, very recently, and it has just been approved by the American FDA, we have seen the combination of teclistamab and daratumumab in early relapse, thanks to the MAJESTEC-3 trial. And the results are also, again, very convincing in terms of progression-free survival. We don’t have yet overall survival final results, but again, this is extremely promising given what we have seen in terms of PFS, but also in terms of safety. 

So the obvious question today, if you have a patient in early relapse, should we choose to go for CAR T-cells or should we go for bispecific antibodies? I don’t believe there is a right or wrong answer because we don’t have such head-to-head comparison. Nevertheless, we need to take into account several parameters. First of all, I have to make a disclaimer. The IMW group, the European Myeloma Network, and many cooperative groups in Europe are usually recommending the use of CAR T-cells whenever possible. And that makes sense because it’s a single-shot treatment. It’s highly effective. I think the data are quite convincing already with CAR T-cells. And you don’t need these multiple visits to the hospital, the long-term administration. And from a patient perspective, and we’ve seen this in the trials, we’ve seen this in real life, actually patients prefer in general CAR T-cells because of the subsequent treatment-free interval. But we also need to take into account the fact that if you want to do CAR T-cells, actually it takes time. It takes time because of the manufacturing, the processing, the apheresis process. So you need to take into account the need for bridging or holding therapy, and that can be very tricky because then you have to choose the optimal bridging therapy. And we know already that being able to use an effective bridging therapy is crucial, not only for the efficacy, but also to decrease the incidence of some adverse event side effects, especially, for instance, in cilta-cel, the incidence of the Parkinsonism-like phenomenon. 

Also, we need to take into account that if you have a rapidly progressive disease, an aggressive relapse, actually CAR T-cells may not be the ideal option because there is a waiting time. And of course, CAR T-cells need to be performed in highly specialized centers, and they need a quite complex, sophisticated infrastructure. On the other hand, bispecifics, T-cell engagers are available off the shelf. You can rapidly, almost immediately, use them if they are indicated. But obviously, you have to take into account the multiple hospital visits. This is a chronic treatment over the long term. It has some implications, especially, and this is now well-established, the risk of opportunistic infections can be very high, and it is mandatory in this scenario to use supplementation with immunoglobulins. So actually, you’re not only using bispecifics, but actually you’re using immunoglobulins and all kinds of anti-infectious prophylaxis. So you can appreciate that, although CAR T-cells are recommended as soon as possible now, and we have strong data in favor of using CAR T-cells, actually, we are in the gray zone because not all patients will be able to receive CAR T-cells. And I think at the end of the day, although we may feel it’s becoming complicated, I’m quite optimistic about it because we have now different solutions for different patients. And this is exactly what we would like to achieve, namely to have personalized treatment. And from that point of view, I believe the field is also moving very nicely in the right direction.

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