Physician Dana Farber Cancer Institute Boston, Massachusetts, United States
Introduction: Anti-BCMA CAR T-cell therapy is approved for relapsed and refractory multiple myeloma (RRMM) with two available products (idecabtagene vicleucel, ide-cel and ciltacabtagene autoleucel, cilta-cel). Data regarding long-term toxicities in a real-world population is lacking. We report long-term toxicities in patients treated with ide-cel or cilta-cel at Dana-Farber Cancer Institute/Brigham and Women’s Hospital.
Methods: Patients who received an anti-BCMA CAR T-cell infusion for RRMM between 8/9/2021 – 2/22/23 were retrospectively analyzed. Toxicities were divided into early ( < 30d), late (30—90d), and prolonged (>90d).
Results: Fifty-four patients, median age 66 yrs. (34-79) received cilta-cel (n = 7, 13%) or ide-cel (n = 47, 87%) and were followed for median 158 days (range 29-395). Median number of prior regimens was 8 (3-15). A total of 13 patients (24%) received prior belantamab mafodotin (blmf). Bridging therapy was used in 41 (76%) patients with most receiving alkylator therapy and 4 on continued blmf.
Cytokine release syndrome (CRS) was reported in 76% of patients (G1: n=30, 56%; G2: n=11, 20%) and neurotoxicity in 4 patients (G1: n=2, 7%; G2: n=2, 4%; grade 2: n=2, 4%,). Any-grade cytopenias included: anemia (n=51, 94%), thrombocytopenia (n=45, 83%) and neutropenia (n=45, 83%).
Grade ≥3 (high-grade) early cytopenias included neutropenia (n=14, 26%; G3: 19%, G4: 7%) thrombocytopenia (n=13, 24%; G3: 13%, G4: 11%) and anemia (G3: n=1, 2%). High-grade late cytopenias included thrombocytopenia (n=14, 26%; G3: 19%, G4: 7%), neutropenia (n=13, 24%; G3: 13%, G4: 11%) and anemia (G3: n=3, 6%). High-grade prolonged cytopenias included neutropenia (G3: n=6, 11%), thrombocytopenia (n=6, 11%; G3: 7%, G4: 4%), and anemia (G3: n=2, 4%). Ten patients (19%) had one or more prolonged high-grade cytopenias; the median age of patients who recovered counts was 60 (n=5, 50%) versus 74 for those who did not (n=5, 50%). Supportive care for all 10 patients included: IVIg (50%), G-CSF (40%), darbepoeitin alfa (40%), and romiplostim (30%).
Eleven patients (20%), median age 68 yrs. (51-75) developed nonfatal infections, with 5 requiring hospitalization. Most common infections involved the respiratory tract (n=9, 17%); 5 patients with COVID-19 and 4 with pneumonia. A total of 41 patients (76%) had hypogammaglobulinemia ( < 600 mg/dL), including 9 of the 11 patients (82%) with infections. No treatment related deaths or myeloid neoplasms were observed.
Overall response rate was 85% (n=46) with 65% (n=35) achieving a very good partial response or better, including 26% (n=14) with a complete response. A total of 25 patients (46%) had either progressive disease or started new therapy at data cutoff with 12 deaths due to progression.
Conclusions: This analysis reports less frequent high-grade cytopenias as compared to previous clinical trial data. Number of prior therapies, bridging regimens, and CRS were not found to be predictive of prolonged toxicity.
