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 nirogacestat.
This trial builds on one. The rationale builds on one of the reported mechanisms of resistance to BCMA and belantamab mafodotin. And 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 secretase. 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 belantamab can combine to.
The trial was a combination of these three drugs. We also added pomalidomide to dose cohorts two and three. The dosing schedule was to start with nirogacestat, then add belantamab every three weeks for three cycles, and then every six weeks after that.
For the results, what we saw when we pretreated first with nirogacestat, we then 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 as I said, with pomalidomide as well.
In dose cohort one, which was belantamab at 1.0, we didn't see much—that was a little bit too low. But for dose cohorts two and three, which was belantamab 1.5 and 1.9 mg/kg, six patients were treated. All responded. So everyone achieved a PR or better. There were three patients with a partial response and three patients with a very good partial response.
As for the side effects, we always think about keratopathy with belantamab. We did see that, even though we used lower doses than the FDA-approved levels. Sixty-six percent of patients had an ocular toxicity. Two patients, or 33%, had 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, which caused some GI side effects, primarily diarrhea, which we also could manage with dose reductions.
So, if we summarize the trial, we saw higher response rates at dose levels two and three with pomalidomide. We did see some ocular toxicities. Overall, belantamab is a clinically effective drug, and a lot of these side effects can be managed if we upfront use slightly lower doses and longer dose intervals.
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HealthTree • December 20, 2025