Advancing Survival in Relapsed/Refractory Multiple Myeloma - Episode 7

SKd or SDd for RRMM

Paul G. Richardson, MD: During the last few minutes, Cristina, I would like to take advantage of your expertise and leadership. You’ve obviously led the selinexor-carfilzomib arm, and I’d love to also ask you to comment more on the success of the selinexor-daratumumab arm. Both of these arms are ones that you’ve really led the charge on. You presented a very nice abstract at ASH [American Society of Hematology Annual Meeting] and an updated 1 at ASCO [American Society of Clinical Oncology Annual Meeting] this year. I’d love your take on that.

Also, I remember very well the EHA [European Hematology Association] presentation last year on selinexor plus daratumumab. And you provided updates on that at ASCO this year. Perhaps in the last few minutes you can walk us through both of those experiences, and then we’ll wrap up from there?

Cristina Gasparetto, MD: Yes, absolutely. These are 2 additional arms of the STOMP trial. I can start with the daratumumab combination. We are ready to publish the results of that arm. We completed accrual. You know, I was surprised by the tolerability of this combination. As you know, daratumumab is probably the most tolerable drug we have in myeloma, with the exception of the early infusion reactions. Coming out as a subcutaneous administration is beautiful for convenience for patients and is very effective. I enrolled a lot of patients on this arm, and I was, as I mentioned, surprised by the tolerability of the combination. Some of the patients were able to sustain the response for a prolonged period of time, even patients for whom I had to decrease the selinexor dose to a lower dose because of toxicity.

The overall response with this combination was in the 70% range, with a clinical benefit of close to 80%. All patients were able to achieve a rapid response and there was, as I mentioned, a sustained response for some of the patients. We were able to show the follow-up data at ASCO. The progression-free survival was about a year with this combination, and the overall survival was not reached yet. But we were able to maintain some of these patients on therapy for a prolonged period of time.

With this combination there were only 2 patients of 34 who were exposed to prior daratumumab. One patient maintained stabilization of the disease, and 1 patient unfortunately progressed. So we really don’t know if this combination can be offered to patients who were exposed to daratumumab before.

But that is not the case for the other formulation, the selinexor-carfilzomib. We also updated our results at ASCO this year. Again, the proteasome inhibitor is delivered in this combination once a week at the recommended phase 2 dose. It was 56 mg, with selinexor given once a week at 80 mg. Again, we were able to achieve a very good response—on the order of 70%. Actually, one-third of patients achieved a very good partial response. We had some patients achieve complete remission.

Again, the same type of toxicity, but mitigated by the fact that the selinexor was delivered once a week. The once-a-week administration is tolerable. Fifty-eight percent of patients were daratumumab exposed, and some were daratumumab refractory. Despite that, we didn’t have any changes in the response. We were very excited to see that this could be a combination that could be given to patients who had failed the CD38-targeting antibody, still maintaining very good responses with this new backbone. So this is another very exciting combination. We’re still finishing the expansion phase on this combination, so hopefully we’ll have more data. But both the daratumumab-selinexor and the carfilzomib-selinexor combinations were relatively well tolerated with the weekly administration of selinexor.

Paul G. Richardson, MD: Yeah, those are fantastic data. I’m so pleased to see you bringing forward the construct of selinexor combined with carfilzomib and, potentially, pomalidomide after daratumumab failure. In other words, when daratumumab fails a patient, what do we have? While daratumumab is a fabulous antibody, as you pointed out, unfortunately once daratumumab runs out of benefit for a patient and fails a patient, we really face a challenge. I’m particularly excited by your project, Cristina, looking at selinexor combined with carfilzomib, pomalidomide, and dexamethasone in various iterations, as we’re discussing and developing right now. That could be a very important go-forward.

Transcript edited for clarity.