Targeting CD38 in Patients With Relapsed/Refractory Multiple Myeloma - Episode 3

ICARIA-MM Phase III Trial Overview

Adriana Rossi, MD:The ICARIA-MM trial has recently given us data with isatuximab in combination with pomalidomide and dexamethasone. And it’s phase III data comparing it to a pomalidomide and dexamethasone backbone. I think there are good preclinical data and phase I data to show synergy of the combination, and the use of pomalidomide, again in affecting the NK [natural killer] cells’ and T-cells’ compartments, as well as the tumor itself.

It’s interesting to see. We had a benefit in progression-free survival [PFS] and certainly deeper responses, which we should expect. I think the control arm did better than it has done in other studies. However, these patients did have fewer lines of therapy compared to some of our other data, so it’s hard to compare between them.

It’s still a PFS of 11.5 versus 6.5 months, it’s clearly significant. And again, it’s a fairly tolerable regimen. The toxicities were really mostly hematologic, which as hematologists, I think we’re capable of managing, other than the infusion reactions as I mentioned. Interestingly, we don’t need as much premedication for this antibody as we do for the daratumumab.

As commonly seen in many of the regimens we use targeting the bone marrow, hematologic toxicities were most common, but really adequately managed with growth factor support and with dose modifications. There were certainly dose reductions in both the pomalidomide and dexamethasone dosing. No changes to the isatuximab dosing, and this was seen in both arms. Certainly a little more frequently, but again I think it’s expected that you would have more cytopenias in a triplet than a doublet. That would be seen with any of our current combinations.

It was nice to see the abstract this year specifically looking at a subgroup analysis of the elderly patients in the ICARIA-MM study. We did see that the benefit in response was the same or even better in the older patients, and not surprisingly the toxicities were also slightly greater. Nothing out of the ordinary. I think we required a few more discontinuations and dose reductions and it was seen in both arms, a little bit more frequently in the older patients, as expected with any triplet or doublet regimen.

Transcript edited for clarity.