IMS 2026 | Prior anti-CD38 exposure and outcomes with isatuximab in R/R multiple myeloma

Maybe it’s important to take into account that this was a post-hoc analysis. So the IRAKLIA trial was designed to assess the non-inferiority of the subcutaneous isotuximab versus intravenous isotuximab in the combination with POM and DEX in the refractory setting, and that was the primary endpoint. However, in this trial, patients exposed to previous anti-CD38 antibodies were not excluded. Even those that were refractory to anti-CD38 antibodies were not excluded, taking into account that there had to be a washout period from one anti-CD38 to the next one. So we had the opportunity to assess a very important question today is if a patient that has been exposed to anti-CD38 antibodies could be exposed again and having some efficacy there. For example, MajesTEC-3 is a combination of teclistamab and daratumumab in which we don’t really know if we can include patients previously exposed to anti-CD38 antibodies, so it’s an important question. So, as the design of the IRAKLIA trial was like this, that you could include patients previously exposed, there was this post hoc analysis in which it was assessed if prior exposure to anti-CD38 antibody impacted efficacy. What were the results? Basically, the main, the most important result, which probably was the most obvious one, is that patients that had not been exposed to anti-CD38 antibodies fared better, much better than those that had been exposed before. That’s an important fact that has, I believe, should be extrapolated to any other trial or any other clinical situation we face nowadays. The second and probably most surprising one is that there were, in fact, no differences between patients exposed, but not refractory, and refractory patients to anti-CD38 antibodies. That’s important. So the fact that the relapse was under treatment or later after treatment was not that important. Those patients did worse with the re-exposure to the anti-CD38 antibody but the thing that we saw that the more time it had passed from the exposure to the from the first exposure to the next exposure impacted results. So patients that had been free of anti-CD38 antibody treatment for more than two years were better than those that had been free of anti-CD38 antibody treatment for less than two years, far better than those that had been exposed closer in time. That means basically that patients naive to anti-CD38 antibody are those that are really sensitive to the drug. The others are not as sensitive, but the more time it lapses between one exposure and the other, the better in terms of efficacy for the patient. And probably those patients that had the longest period between exposures are also patients that had some treatment in between, so probably there was also a change in the subclones or whatever that allowed a re-sensitization to the antibodies, but never to the extent of patients that are naive. And that’s probably the most important message here.

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