IMS 2025 | Two types of resistance to BCMA-directed treatments in multiple myeloma: how do they differ?

There are two types of resistance and we need to be careful because often they are mixed up and that’s how it can alter our understanding of the data. There are the refractory patients or the ones that do not respond, which is usually 20-30% of patients, which means either you are refractory or you don’t respond well and after, you know, five, six months you have to change therapy. So those patients we think and our data point out already have genomic alterations that promote resistance. So the mechanism of resistance is already there and most of the time is genomic complexity, genomic instability, promoting masses, promoting exhaustion, and lower CAR-T expansion. On the other hand, the one that responds and then progresses, we showed recently in collaboration with the Kiel University, particularly Paola Neri and Nizar Bahlis, that these alterations that are acquired are acquired after 6-9 months and then selected later on. And these alterations are treatment-specific, which means that if you get one of these alterations, you might still respond to another specific antibody. So relapsing after one product doesn’t mean you will be refractory to another. But I think we need really large data sets, characterizing all these patients to identify the right sequence, because now myeloma has one good problem to have, but it’s still a problem, that is, we have too many drugs. So we have to decide which is the first drug, the second drug for each patient. Some patients may benefit first from a CAR-T, others from a BCMA-specific, others from BCMA, others GPRC5D or FcRH5. So I think there is a lot of work to do in these settings. And I think genomics, comprehensive genomic profiling, and large collaborative networks are the answer to that.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.