Real-world outcomes with BCMA- and GPRC5D-targeting bispecific antibodies in plasma cell leukemia

ABSTRACT: Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell-redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as active (≥5% circulating plasma cells within 30 days before BsAb initiation) or historical. Patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging to CAR T-cell therapy (Tal Bridge, 11%). Cytokine release syndrome was grade 1 to 2 in 56% and grade 3 to 4 in 4% of patients, whereas neurotoxicity was grade 1 to 2 in 16% and grade 3 to 4 in 5% of patients. The overall response rate was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS values of 1.2 and 1.6 months and mOS values of 8.1 and 3.6 months, respectively (P = .007, P = .023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months vs 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P< .001, P = .002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were well tolerated in PCL, with talquetamab showing superior outcomes compared with B-cell maturation antigen-directed BsAbs.