ciltacabtagene autoleucel 治疗复发/难治性多发性骨髓瘤：CARTITUDE-1（II 期）日本队列

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 2 ) and fludarabine (30 mg/m 2 ), patients received a single cilta-cel infusion at a target dose of 0. 75 10 6 (range, 0. 5-1. 0 10 6 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 -5 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.