Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort.

Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE-1 study of ciltacabtagene autoleucel (cilta-cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m ) and fludarabine (30 mg/m ), patients received a single cilta-cel infusion at a target dose of 0.75 × 10 (range, 0.5-1.0 × 10 CAR-positive viable T cells/kg). The primary endpoint was overall response rate (ORR; defined as partial response or better) by International Myeloma Working Group criteria. A key secondary endpoint was the rate of very good partial response (VGPR) or better (defined as VGPR, complete response, stringent complete response). This first analysis was performed at 6 months after the last patient received cilta-cel. Thirteen patients underwent apheresis, nine of whom received cilta-cel infusion. Eight patients who received cilta-cel at the target dose responded, yielding an ORR of 100%. Seven of eight (87.5%) patients achieved a VGPR or better. One additional patient who received a below-target dose of cilta-cel also achieved a best response of VGPR. MRD negativity (10 threshold) was achieved in all six evaluable patients. Eight of nine (88.9%) patients who received cilta-cel infusion experienced a grade 3 or 4 adverse event, and eight (88.9%) patients experienced cytokine release syndrome (all grade 1 or 2). No CAR-T cell neurotoxicity was reported. A positive benefit/risk profile for cilta-cel was established for heavily pretreated Japanese patients with relapsed or refractory MM.