SOHO 2026 | Sequencing CAR-T, bispecifics, & ADCs in myeloma: how is the paradigm changing?

So the topic of sequencing is really an evolving field, and the biggest gap in this field is that we don’t have well-conducted design to answer the question of bridging. So there are a lot of potential biological rationales to come up with an ideal sequence. But we don’t have clinical studies that really addressed this point. Another important factor is that the way we use this regimen is changing over time. And we are basing all our information and recommendations on ways to use these regimens and settings that are not the way that we’re using now. So what I’m saying is that we have some real-world data mainly pointing towards the fact that using a CAR-T cell therapy after either an ADC or a bispecific antibody in late lines, when those agents were used until progression, clearly had a negative impact for the use of CAR-T cell therapy and the efficacy of CAR-T cell therapy. So this may still be true if these agents are used until progression in early lines, but we are seeing now more and more the use, for example, of bispecific antibodies, particularly in clinical trials up front, as early as in newly diagnosed patients, with a fixed duration fashion. So that’s this paradigm of bispecific antibodies impairing the efficacy of CAR-T cell down the road. Also, when those agents are only given for a limited duration of time, we don’t know. So I would say that to make things simple, at least now, if a patient is eligible to receive CAR-T cell therapy in a second line, I would say that it would be safe to advise those patients to receive CAR-T cell therapy before receiving a bispecific antibody or an ADC, particularly those targeting the same target of the CAR-T. So, for example, for cilta-cel, I would advise to receive CAR-T cell therapy first, provided that the patient is eligible, but also provided that the disease is, let’s say, eligible or in a shape to ensure safety and efficacy for the CAR-T cell. With the use of bispecific antibodies in early lines and with the data that we’ve seen from, for example, MajesTEC-3 and MajesTEC-9, now the bar is higher for CAR-T and for recommending CAR-T cell therapy. And we need to make sure that we are offering CAR-T cell therapy to the right person at the right moment. So I think that we still advise to use CAR-T cell therapy, but making sure that we are recommending this to the right patient at the right stage of the disease.

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