ASH 2021 | Subanalysis of the KarMMa Trial: Predicting complete response to CAR-T in multiple myeloma
Nina Shah, MD, University of California, San Francisco, CA, discusses findings from a subanalysis of the Phase II KarMMa trial (NCT03361748), which assessed idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)–directed (chimeric antigen receptor) CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma. The aim of this subanalysis was to identify predictors of complete response. 128 patients received ide-cel, with the primary and secondary endpoint being overall response rate and (stringent) complete response (CR/sCR) respectively. In a subanalysis of the KarMMa trial, which attempted to elucidate factors affecting CR/sCR, presence IgG and serum BCMA negatively affected CR/sCR, whereas a high vector copy number in drug was associated with a high CR/sCR. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
This is a nice sub-analysis of the ide-cel KarMMa Trial, which was the pivotal single-arm Phase II trial, looking at bb2121 BCMA directed CAR-T cell therapy for multiple myeloma. Now we already know for that trial, that the overall response rate was around 73% and at the highest doses, the median PFS was about 12 months. And we know that patients who achieved a CR actually did very well with a median PFS of 20 months...
This is a nice sub-analysis of the ide-cel KarMMa Trial, which was the pivotal single-arm Phase II trial, looking at bb2121 BCMA directed CAR-T cell therapy for multiple myeloma. Now we already know for that trial, that the overall response rate was around 73% and at the highest doses, the median PFS was about 12 months. And we know that patients who achieved a CR actually did very well with a median PFS of 20 months. So we want to understand better what predicts for complete response, because we want to send patients to this therapy if it’s going to work. And so an analysis was done, a separate analysis to try to identify baseline correlates, which would potentially predict for complete response. And in this, we were able to see by a multivariate analysis that the serum BCMA, as well as IgG subtype and prothrombin time or INR were actually negative correlates for a complete response, meaning the higher that those were the less likely a patient was to have a complete response.
And vector copy number was actually associated with a better response. A vector copy number in the drug product, which suggests a couple of things. One that if a patient is sicker with higher tumor burden, they’re probably less likely to have a complete response. So a lot of our heavily pretreated patients who have maybe exploding disease, maybe those people are not the ones that we should take to CAR-T or to ide-cel in general. But we should maybe think about out doing it earlier before their disease becomes too uncontrolled.
That’s probably reflected by the serum BCMA. And I think it also reflects that there are some people that have better expansion or drug product based on how their transduction goes and the culture process. And that’s a little bit harder to determine what goes into that from the apheresis product, but that is something that is probably going to be investigated and better understood from other CAR-T products. Overall, I think it’s really important for us to be able to predict who’s going to do well or not. This is an expensive therapy and does take a lot of patient time up front and it can be very effective. So if we can find out how patients can do best, I think that’ll be better, serving the entire community.
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