Trial Data Review: Selinexor, Carfilzomib, and Dexamethasone in R/R MM
Dr Mikhael reviews the baseline characteristics, study design and key efficacy and safety data of selinexor, carfilzomib, dexamethasone (XKd) in patients with relapsed/refractory multiple myeloma who are non-refractory to carfilzomib.
Joseph Mikhael, MD: This agent proved itself as a single agent, as I've mentioned, with dexamethasone in heavily relapsed setting but today we're going to be evaluating it in combination. This article that we're featuring today is a part of the larger STOMP study where selinexor was being partnered with multiple other agents. In this case, it's being partnered with carfilzomib, a potent proteasome inhibitor in patients with relapsed myeloma. When we look at the baseline demographics of these patients that were treated, we really see quite a range within age and performance status but in particular, we notice that the significant majority of them have recently had daratumumab, and indeed over half of these patients have high-risk disease. When we look at the key high-risk features of deletion 17p, the translocations 414 and 1416 and gain 1Q together, 53% of the patients on the study did indeed have high-risk disease. The study was designed to determine the maximum tolerated dose and the recommended phase 2 dose going forward. As you can see here, whereas we use selinexor twice weekly at 80 milligrams twice weekly, the starting dose here was 100 milligrams along with 40 milligrams of dexamethasone and 56 milligrams per meter squared IV weekly of carfilzomib. Indeed, we saw that ultimately the MTD and the RP2D was at 80 milligrams of selinexor, 40 milligrams of Dexamethasone, and 56 milligrams per meter squared intravenously once weekly with carfilzomib. With that combination, we really saw rather extraordinary results in that in the 32 patients that were treated, 25 responded so we had a 78% response rate. When we break that down, no surprise because we had a large group of patients from early relapse to late relapse, we do see a high response rate in fewer prior lines at 89% with one to two prior lines, but still 74% in those with a three or more aligned. Similarly, when patients had had less exposure to the three classes of monoclonal antibodies proteasome inhibitors and immunomodulatory agents, we saw actually a hundred percent response rate. In those who were triple class refractory, we saw 67% response rate and indeed an 82% response rate in those that had high-risk disease. The response rate translated indeed into a median progression-free survival of 15 months and a duration of response in those who are responders of just short of 23 months. Now, it's one thing to talk about the efficacy. We have to talk about safety. Of course, one of the greatest concerns we had in selinexor when it was used in late-stage myeloma was the nausea that it causes. Sometimes I think of it as what I call head nausea and stomach nausea. The stomach nausea is what we're used to, where people feel like they're going to throw up. The head nausea is more of my teenage daughters on a Saturday on the weekend. They just don't want to get out of bed. There's this anorexia feeling. There's this, we don't want to engage very much. We found that when we've shifted this drug from twice weekly to once weekly, that considerably improves. We do still see significant cytopenias as you can see here. Although granted the majority are grade one and two. We don't see as many grade three. Similarly with nausea, it is very common where nearly 78% of people experience nausea but we do also see that this nausea is much lower grade than what we had seen in prior and we're going to talk a little bit about how Dr. Kaya manages this in his practice so that we can minimize this.
