Source: Myeloma – Hematology Advisor
BCMA-directed chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies can produce transient responses in patients with multiple myeloma (MM) whose disease relapsed on prior BCMA-directed CAR T-cell therapy, according to research published in Blood Advances.
Researchers performed a retrospective analysis of 68 MM patients whose disease had relapsed after BCMA-directed CAR T-cell therapy. The patients had received CAR-T cell therapy on a clinical trial (n=48), commercial idecabtagene vicleucel (n=17), or commercial ciltacabtagene autoleucel (n=3). Overall, the patients had received a median of 7 prior lines of therapy (range, 1-14).
There were 58 patients who started another line of therapy after relapse on CAR-T therapy. They received a median of 2 salvage lines of therapy (range, 1-8).
The overall response rate (ORR) after first salvage therapy was 41%. The most common first salvage therapies were alkylator-containing therapy (n=13), CD38-based combination therapy (n=11), BCMA-directed bispecific antibodies (n=6), belantamab mafadotin (n=4), and CAR-T therapy (n=1). The median time spent on first-line salvage treatment was 2.2 months.
There were 34 patients who received at least 1 line of salvage BCMA-directed therapy after CAR-T relapse. The ORR was 55% in this group overall, 89% in patients who received another BCMA-directed CAR-T therapy, 60% in patients who received BCMA-directed bispecific antibodies, and 11% in patients who received belantamab mafadotin.
The median duration of response was 8 months with subsequent BCMA-directed CAR-T therapy, 4.4 months with bispecific antibodies, and 2.8 months with belantamab mafadotin. The median progression-free survival was 8.3 months, 3.6 months, and 1 month, respectively.
There was a trend toward improved overall survival (OS) in patients who received BCMA-directed CAR-T therapy or bispecific antibodies within 6 months of relapse. The median OS was not reached in these patients and was 16.5 months in patients who did not receive BCMA-directed CAR-T therapy or bispecific antibodies (P =.06).
“Our study shows that a variety of treatment regimens can be effective in eliciting hematologic responses after CAR-T therapies, including for classes of agents that patients were previously deemed refractory to,” the researchers wrote. “However, response durations continue to be limited. Novel therapies targeting new antigens continue to be needed for this patient population, and further studies are needed to determine the optimal sequencing and combinations to use in conjunction with BCMA-directed CAR T-cell therapy and after BCMA-directed CAR-T relapse.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.