IMS 2026 | Daratumumab plus bortezomib maintenance in TI NDMM: insights from ALCYONE and GEM OPTIMAL

The Spanish myeloma group designed a trial called the GEM OPTIMAL trial in which we tried to find the main reason why there were so many differences between the outcomes in the ALCYONE trial where patients received daratumumab, bortezomib, melphalan, and prednisone, and the MAIA trial where patients received daratumumab, lenalidomide, and dexamethasone. We believe that the main difference was that patients in the ALCYONE received maintenance with only daratumumab, while patients in the MAIA trial received daratumumab and lenalidomide indefinitely. And this perhaps is one of the biggest reasons that there was such a big difference in terms of progression-free survival. So what we did is a trial called the GEM OPTIMAL trial where patients that received an induction as in the ALCYONE with Dara-VMP, and later on their physicians decided to give them a double maintenance with daratumumab and bortezomib and see whether the addition of the bortezomib improved outcomes for these patients. So this was a cohort of patients non-transplant eligible. And what we saw is that at the three-year mark, which is the one we are presenting here, is that while in the ALCYONE trial, almost 46% of patients had progressed during the first three years of maintenance, we have only seen 36% of progressions in a much frailer population. The ALCYONE trial had a population with a median age of around 60 years, while we have a median age of close to 80 years old. So a much frailer population. Sorry I said that the ALCYONE was 60, it’s 70 years old. So much frailer population, with better outcomes. We think that this may impact positively to the options physicians have, especially in countries where not all of the drugs are available, and especially because many of the times, lenalidomide is not adequately tolerated by patients. So, at this time, we are starting to have a lot of data regarding minimal residual disease. We know that with this type of treatments, the numbers of patients that might achieve negative minimal residual disease might be less. So, with this type of maintenance, having received this type of induction, perhaps patients will have an indefinite maintenance. It is very important for the physicians, in this case given that the treatment is monthly, it’s daratumumab and bortezomib once a month, to be very aware of infections the patient might have, which was the most frequent adverse effect, and also to be very aware of the peripheral neuropathy that bortezomib can cause. If there is any sign, do a dose reduction. But our experience has been that patients have tolerated it very well.

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