My name is Malin Hultcrantz and one of the attendings in the myeloma service at Memorial Sloan-Kettering in New York, and this year at ASH, I'll be presenting a poster on our investigator initiated trial on belantamab, pomalidomide, and mirogacestat.
This trial builds on one. The rationale builds on one of the reported mechanisms of resistance to BCMA and belantamab mafodotin. And is that is that BCMA which is expressed on the cell surface is cut off or shed from the cell surface by an enzyme called gamma securities. So the rationale here is to do a combination with a gamma secretase inhibitor called nirogacestat. So we will have more BCMA on the cell surface that than belantamab can combine to.
So the trial was a combination of these three drugs we ordered that also added pomalidomide to dose cohorts two and three. And the dosing schedule was to start with nirogacestat than add belantamab every three weeks for three cycles and then every six weeks after that.
So for the results, what we saw when we pretreated first with nirogacestat, we then we looked at the BCMA expression before and after this pretreatment. And we saw that for most patients, we actually saw a significant increase in the BCMA on the cell surface. So we then treated with belantamab. And then as I said with pomalidomide as well.
So in dose cohort one, which was belantamab at 1.0, we didn't see that was a little bit too low. But for a dose cohort two and three, which was belantamab 1.5 and 1.9mg/kg, there's six patients that were treated. All responded. So everyone achieved a PR or better. So there are three patients with the partial response, three patients with a very good partial response.
As for the side effects, we always think about the keratopathy with belantamab. We did see that also, even though we used to have lower doses than the FDA approved levels. So we did see 66% of everyone had an ocular toxicity. There are two patients, so a 33% higher grade three. All of these resolved either to grade zero so complete resolution or to grade one.
The other side effect that we saw was from nirogacestat is that where we saw some GI side effects, primarily diarrhea, which we also could manage them with dose reductions.
So if we summarize the trial. So we saw, higher response rates and the dose levels of two and three with pomalidomide. We did see some of the ocular toxicities. And I think that overall belantamab is a clinically effective drug. And I think a lot of these side effects can be managed if we upfront use a bit lower doses and longer dose intervals overall.
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HealthTree • December 20, 2025