Ross Firestone: Antigen escape with BCMA-targeting therapies in multiple myeloma
Ross Firestone, Hematology/Oncology Fellow at Memorial Sloan Kettering Cancer Center, shared a post on X about a recent paper by Saad Usmani et al. titled “Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma” published in Blood Journal.
Authors: Ross Firestone, Nicholas Socci, Tala Shekarkhand, Saad Usmani, David Chung et al.
“Our work with Saad Usmani and David Chung at Memorial Sloan Kettering Cancer Center looking at antigen escape with BCMA-targeting therapies in multiple myeloma patients is now out in Blood Journal.
We found that loss of BCMA expression can (rarely) be seen after BCMA CAR T cell or belantamab mafodotin treatment and limits future response to BCMA-directed CAR T cells and bispecifics. It can be detected by IHC before therapy selection.
BCMA expression loss in MM had not previously been reported after belantamab treatment, which we found to be due to biallelic loss of the BCMA gene, TNFRSF17.
Interestingly, prolonged exposure to belantamab wasn’t necessary for antigen loss, as we observed it after only 2 months of therapy in one case.
This has implications for BCMA-directed therapy sequencing, especially following the results of the DREAMM-7 and DREAMM-8 trials, as belantamab may become more frequently used in earlier lines of treatment.
We also found that, at times of active disease, low or undetectable levels of soluble BCMA reported on expression loss, offering a noninvasive method to test BCMA expression in clinical practice settings.
Thanks to the investigators and to our patients for help with this work!”
Rahul Banerjee, Assistant Professor at the University of Washington, shared this post, adding:
“Congrats Ross Firestone, Saad Usmani et al. on fascinating multiple myeloma work in Blood Journal!
Time-based thresholds to sequence BCMA will go extinct someday…
Holly Lee and Nizar Jacques Bahlis have previously shown power of WGS to predict recurring response – maybe similar with BCMA IHC and even sBCMA?”
Sources: Ross Firestone/X and Rahul Banerjee/X
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