ASCO 2026 | The evolving role of isatuximab in myeloma: mechanisms, combinations, and future directions

Well, I think isatuximab is an important, is a very important CD38 monoclonal antibody. I think it obviously in the right combination works after prior daratumumab has failed. For example, in this study, one could have been daratumumab exposed and in fact patients were allowed to enter the study even if they were refractory to daratumumab as long as the interval was six months. I think it’s important to recognize that isatuximab has different mechanisms of killing in the sense that both of them target CD38 but critically isatuximab binds to a different epitope and it’s more dependent on direct killing as opposed to daratumumab, which relies on complement-mediated killing to do its work. With all of that in mind, there are qualitative differences between the antibody, in my opinion, and in the clinical studies, I think we see a hint. Both are great antibodies, but at the end of the day, there’s a 1q amplification signal for patients receiving isatuximab that I’m personally impressed by. Dara works in 1q amplified disease, but I personally feel that 1q amplification perhaps is better partnered with isatuximab. So I think there are a variety of reasons to think about isatuximab, not least after dara has been previously used and or failed, but also even in the upfront setting, actually, Tom, I feel that in the 1q-amplified population, for example, there is a reason to think about isatuximab as an important choice. And the data at the phase 3 level that supports its use is no less than IMROZ, the randomized Phase III trial led by Thierry Facon, which really is quite striking in terms of results. But I don’t want in any way to say that daratumumab doesn’t work in 1q disease. That’s not true at all. It does. And the CEPHEUS results show that. But I think there may be an edge, as it were, to isatuximab in that setting, which is potentially very relevant. And that being said, obviously, we’re very pleased with the performance of isatuximab in combination with other agents. Our own work has been with RVd, isatuximab, as well as ISABELA and other settings. So we’re very pleased with it as an effective antibody. One very important other point to make is it’s now being made available through an on-body infusion device, so-called OBI. And that, I think, will be an important practice-changing approach, which will allow patients and providers that much more convenience. In that spirit, we’re combining isatuximab with Iber-Vd in a prospective trial led by my colleague Dr. Wixing Liu. And in the DETERMINATION-2 study, which is being led by my colleague Dr. Clifton Mo, we’re about to launch Iber-Vd plus isatuximab in a large randomized Phase III setting.

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