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

Abstract

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/m2) and fludarabine (30 mg/m2), patients received a single cilta‐cel infusion at a target dose of 0.75 × 106 (range, 0.5–1.0 × 106CAR‐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.

Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma

“…Ciltacabtagene autoleucel (Cilta-cel, previously known as LCAR-B38M) is a biepitopic CAR-T product targeting BCMA antigen, and has achieved remarkable success in the treatment of relapsed/refractory (r/r) MM patients in China 3 , 8 , 9 and United States of America (US) 10 . In light of it, Cilta-cel successively obtained approval from the US FDA, the European Medicines Agency, and the regulatory agency of Japan 11 recently.…”

Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121) in Japanese patients with relapsed and refractory multiple myeloma

“…This sub-analysis of KarMMa is one of the first studies, along with the sub-analysis of CARTITUDE-1 [ 16 ], to evaluate the safety and efficacy profile of a CAR T cell therapy targeting BCMA in Japanese patients with RRMM. All Japanese patients who underwent leukapheresis successfully received ide-cel infusion.…”

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

“…Infections: Based on data from 17 studies, the overall proportion of any grade of infection was 45.36% (95% CI, 33.89-57.05; I 2 = 86%; Figure 7), and the proportion was 17.52% (95% CI, 7.91-29.43; I 2 = 81%; Figure 8) for ≥grade 3 infections among 11 included studies. [29,33,35,[37][38][39][40]42,[44][45][46][47]49,50,53,55,56]. [29,33,35,[37][38][39][40]42,[44][45][46][47]49,50,53,55,56].…”

“…[29,33,35,[37][38][39][40]42,[44][45][46][47]49,50,53,55,56]. [29,33,35,[37][38][39][40]42,[44][45][46][47]49,50,53,55,56]. All-cause mortality: Data regarding mortality from all causes were outlined in 28 studies, resulting in a cumulative mortality rate of 23.34% (95% CI, 16.57-30.79; I 2 = 78%; Figure S2M).…”