iwMyeloma 2026 | Early use of immunotherapy in myeloma: TecDara, bispecific consolidation, and alpha emitter therapy

Faith Davies:

My name is Faith Davies and I’m currently at iwMyeloma 2026 in Miami and we’ve just finished an amazing session about the use of immunotherapies for the treatment of multiple myeloma and so I’ve been joined by a number of my esteemed colleagues who have kindly offered to summarize some of the interesting things about their talks. So I’m going to start off with Marc. If you want to introduce yourself and just tell us a little bit about what you had to say today.

Marc Raab:

Yeah, my name is Marc Raab. I’m from Heidelberg, Germany, heading the Myeloma Center there in the German study group. And I had the topic tec-dara in combination, especially for high-risk myeloma patients, and took the chance to take a deeper look in our own trial where we use tec in combination with dara and len in frontline transplantation where we see very, very high response rates, MRD negativity rates in patients who were tested. Overall, we have only one patient who was never tested because no sample was available. So, summarizing a cumulative MRD negativity rate of 98% by the end of induction. And when we dig a little bit deeper now, very preliminary data on 13 patients with high-risk myeloma, according to the new definition, IMWG definition, we found that 12 out of the 13 patients actually had a sustained MRD negativity of 12 months already achieved now. And the one patient was sort of an early dropout, so he could not obviously achieve a sustained MRD negativity. So that was, I think, the more exciting look into the future of myeloma in a high-risk setting.

Faith Davies:

Yeah, no, I mean, for me as an audience member, just seeing those graphs where there’s like, you know, your response kind of blocks and it’s like 100% is really impressive. And I think it was like 50 patients you have with kind of different combinations of bispecifics with the traditional chemos in there, is that correct?

Marc Raab:

Yeah, so that’s what we so far have evaluated, the 49 patients exactly, were all tec-based. We have arms with tal, we have arms with [unintelligible], but the analysis set so far is the tec-based arms. And so, the combination with dara and len, all of them, and about 20 patients had also, in addition, bortezomib and induction therapy. It’s a tec-dara-VRd-based PERSEUS-like approach.

Faith Davies:

No, it’s really interesting, and it’s going to be fascinating to see where we go with this, having had such incredible results of things. So I want to congratulate the German study group. So thank you so much for that data. Dickran, you presented some other cool data around the immunotherapy space, but in a slightly different setting. Do you want to tell us a bit about that?

Dickran Kazandjian:

Sure. So the focus of my talk was our IMMUNOPLANT study, where we try to see if there’s a role of the bispecific antibody, linvoseltamab, right after the initial induction phase. So not part of the initial combination, but in a subset of patients afterwards. So for our eligibility, we decided to use those patients who had a very good partial response or better, but just didn’t make it to the end in terms of MRD negativity at 10 to the minus 6 sensitivity. And so we enrolled those patients. We enrolled about 25 patients, and 20 patients were evaluable. And we saw in all 20 patients, they obtained MRD negativity at 10 to the minus 6 by NGS and by flow. The majority of those patients actually attained it after a fixed course of four cycles of treatment. Two patients needed an extra two cycles. But the trial was written in such a way where we did not want to use indefinite bispecific and the max was only six cycles. And I guess even more importantly, I think it’s important, the depth of response we keep talking about that, that’s obviously important, but what’s really more important in terms of getting to a functional cure is sustainability. So we had the six-month, because it’s an early study, the six-month milestone ten patients were evaluable for it and all ten were able to maintain their MRD negativity. So we’re optimistic, that’s why we’re going to expand the study and really try to get a precise sustained MRD negativity rate at 12 and 24 months and see if this could potentially be a new alternative to the paradigm in newly diagnosed myeloma.

Faith Davies:

I think you’re right. One of the interesting things that the audience was excited about was the fact that the such high MRD negativity rates and this potential of cure, and then kind of, I think everybody took it as a given that both approaches are great. And there was some discussion about, do we put everything up front? Do we do traditional chemo followed by the immunotherapies and how we should kind of go forward? And I think, you know, Marc, you made a great point about that we need to go in potentially hard and once we’ve solved the problem, then potentially come back a little bit. I don’t know if you want to comment a bit more.

Marc Raab:

Yeah. So I think like learning from the Hodgkin guys a little bit, right? So push as far as you can to really get cured almost all patients and then start cutting back. And I think where we should now already start cutting back is in the duration of therapy because we all think that’s the biggest burden on the long run for patients. And then once we are there, we know, okay, maybe, I don’t know, two years, three years, we don’t know yet, right? For most patients, maybe enough of therapy, of intensive therapy. Then I think it’s time to really start cutting back, at least for those patients where we see that’s enough, right? And maybe we can, again, spare tox and release some of the treatment burden in addition, and we should start exploring that now, but in parallel. But I think to really draw solid conclusions, we need to get to this, you know, almost 100% cure rate, which is a big word, I know, but that’s, I think, what we’re aiming for.

Faith Davies:

I think both studies show the power of MRD, though, don’t they, and how important that is. So then we moved on to the kind of relapse setting, and we moved our immunotherapy agents a little bit. So can you tell us a little bit about what you had to talk about?

Yi Lin:

Yes, absolutely. I’m Yi Lin from the Mayo Clinic in Rochester, Minnesota, and I’m very happy to share at iwMyeloma 2026 all the updates that we’ve seen with CARTITUDE-4 over the last year. In particular, you know, we’ve had longer follow-up with CARTITUDE-1, which is a single-arm study. So we know, you know, with an average of three-year PFS, about a third of the patients that could stay in remission for five years or longer. We’re now seeing with CARTITUDE-4, which is a randomized control study in one to three prior lines compared to standard of care triplet. So now we’ve had close to three-year follow-up on that study, so you know, more maturation of the PFS and OS data to really see that there is a definite trend for improvement in the PFS rate as these patients are treated in earlier lines. The PFS advantage over standard care triplet is maintained and across all risk groups, and we’re seeing an overall survival advantage. So that’s all very encouraging to see because, you know, for patients in earlier lines of treatment that could be younger, we really have to think about not just the benefit of treatment of myeloma, but overall quality of life with that particular treatment modality. So we’re also seeing that improvement in patient-reported quality of life and outcome as well. And I think the other thing that is interesting to consider in the context of all the great therapies that are coming into early lines of therapies as well is, you know, CAR-T being a very individualized immunotherapy. So really trying to learn from some of these immune profiles for patients, you know, in earlier disease setting versus later. So corresponding to what we’re seeing with the clinical outcome, suggestions that we’re seeing, you know, more naive, potentially more fit T-cells and the myeloma microenvironment having less suppressive signals. So all of that seems to agree with what we’re seeing with the clinical outcome.

Faith Davies:

Yeah, I think that’s what struck me was that we’ve kind of, there appears to be the whole package there with the CAR T-cell and the fact that we’ve got our translational correlates, which are suggesting we’re getting a good microenvironment after therapy, but also we’ve got the overall, the progression-free, and as you say, the quality of life coming in together as well now. So it’s exciting and it’s difficult times now because we didn’t really get into it in the session, but do you go bispecific? Do you go CAR? And I think that’s probably a whole discussion for another one of these. And then, Damien, you presented some real cool data as well about other alternative approaches.

Damian Green:

Yeah, well, thank you. And, you know, I’ll say, I’m Damian, the chief of the Division of Transplant Cell Therapy at the University of Miami Sylvester Comprehensive Cancer Center. And, you know, I did present work using our alpha-emitter therapy and radio-labeled antibody therapy directed against myeloma. We know that multiple myeloma cells are exquisitely radiosensitive. We also know we’re in a space where, look, as has just been discussed, there are lots of very effective and exciting forms of immune-based therapy of myeloma. Still, in my clinic, and I’m sure in all of our clinics, unfortunately, at least for now, we continue to see patients relapsing who come in with limited options, and I think we have to have a relatively broad arsenal of possible approaches. So this approach allows us to specifically target radiation to myeloma cells, and alpha emitters in particular, something that only a small number of groups, and you know, have not been fully explored until very recently, there is now a lot of excitement about these because we can finally put them on antibodies stably and deliver them to target, and they pack a whopping punch, but over a very short distance only one cell diameter, maybe two. So in that way, and the data that I showed just demonstrates that perhaps this could be integrated in places like minimal residual disease positive or early relapse settings, especially if we see escape where we start to see loss of antigen, one antigen or another. These are, you know, these approaches, as long as the CD38 or whatever antigen we’re targeting is still on the cell, they’re kind of agnostic to some of the ongoing changes within the cell. So that, I think, was promising. And in particular, we showed recent data in lymphoma, but I think it applies to myeloma as well, where we can combine the approach of using the radiation with immune checkpoint inhibition in an immunocompetent model, and thereby elicit a strengthened response, even against cells that may be antigen negative. And we demonstrated that using this approach in lymphoma, but the same thing could be true in myeloma. So if you actually target some of the cells with radiation that still have antigen and others have lost it, we’re able to demonstrate that even those antigen-negative cells will respond if you add an immune checkpoint inhibitor. And I think that might potentially be something promising for future integration into care.

Faith Davies:

That’s just amazing. And I think you mentioned in the meeting how these radio-labeled approaches have kind of come back into fashion after the prostate kind of experience and so on.

Damian Green:

Absolutely, yeah, both in neuroendocrine tumor and in prostate. I think it rekindled, you know, the earliest place, as often happens, I’d say, in sort of pioneering work in the malignancies. We often see things happen in the hematologic malignancies first for a number of reasons, but I think that’s just the case. We saw many years ago targeting of lymphomas, let’s say, some targeting of leukemias using radio-labeled antibodies, but in a pretty crowded space, and I’d say imperfect systems. I think now we’re at a point in sort of drug development, in our understanding of the immune system, that we can take a leap forward in terms of actually using radiation in ways that I think can be more refined, specific, and integrated into our care.

Faith Davies:

Excellent. Thank you, everybody, for joining me and for chatting about that session. And thank you to the audience for listening to us. We’re going to sign off from iwMyeloma 2026. Thank you.

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