ASH 2025 | Phase II REVIVE trial: teclistamab plus daratumumab for high-risk smoldering multiple myeloma

The REVIVE study is a new study that we have opened at the University of Miami. I’ve been involved, I think I have done six studies so far for smoldering patients, for high-risk smoldering multiple myeloma. We were the first to develop a three-drug combination with KRd for smoldering multiple myeloma almost 15 years ago. And then there have been KRd with transplant and have been KRd with CD38 targeted antibodies. In our first study with just KRd alone, we now have very long follow-up. We have over 10 years of follow-up. And we have seen that approximately 70% of patients remain MRD negative even after they have been off therapy for eight or 10 years. So that has given me a lot of ammunition to think that maybe that could be an approach to try to cure the disease. Obviously, we don’t know that, but that has been sort of a hypothesis.
I also was involved in the Centaurus trial. I was the lead investigator, which is the daratumumab, three different dosing scheduled study that was done and completed and published back in 2020. And that was the one that was done as a test balloon for the AQUILA trial. I also served as the chairman for the IDMC, so I monitored the AQUILA trial for all the years, and it just came out in New England Journal in the past 12 months or so. And that led to the FDA approval for daratumumab in November of 2025.
So having seen all the data, followed it very carefully, what was striking to me is how daratumumab can significantly reduce the risk of progression, around 50% round number, reduce risk of progression, which is amazing. And that’s why the FDA approved daratumumab on in this setting of high-risk smoldering multiple myeloma. But looking at the details and looking at all the data we have generated in the past, it’s about 8% of the patients that reach a remission or a CR. And I would guess that we have not tested, but I guess it’s probably maybe 1% are MRD negative or maybe zero. I don’t know. So it’s not a very deep response, but it can hold the disease. So what I was thinking is, could we combine daratumumab with a bispecific antibody and see if it could achieve very deep responses and have high rates of MRD negativity? And I worked for almost 20 years on MRD, and we took it to the FDA last year, and they approved it as an early endpoint for accelerated approval.
So we designed the REVIVE study. We have treated 25 patients at this time. We present here at ASH 2025 how we can give teclistamab and daratumumab once a week for one cycle, and then we give the two drugs once a month. So it’s a very infrequent dosing schedule. And we show that virtually every patient becomes MRD negative 10 to minus 6 within 6 to 12 months. We keep patients on the trial once a month for up to 24 doses. So that’s about two years of therapy. And after that, we will do bone marrow biopsy, we do it after one and two years. And the protocol will call for an annual bone marrow biopsy one year after, two, three, four, and five years after stopping therapy. So this is really a study that is set up to test the hypothesis that you can eradicate the disease, and you can stop the treatment, and you can see evidence of no returning disease up to five years later. So it’s really an attempt to see if this could be a curative approach. We are going to enroll up to 50 patients on the study, so it’s not fully enrolled, but we are very excited about this.

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