Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment

Abstract

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.

Figure 1.

Efficacy of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma with and without renal impairment. Patients who died or progressed before the time point of interest were considered non-responders. Patients who were not evaluable by International Myeloma Working Group response criteria, or when data was not provided or time point not reached were excluded from the denominator. CrCL: creatinine clearance; CR: complete response; sCR: stringent complete response; MRD: minimal residual disease; VGPR: very good partial response; PR: partial response.

Figure 2.

Survival outcomes with idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma with and without renal impairment. PFS: progression-free survival; CI: confidence interval; OS: overall survival; CrCL: creatinine clearance; min: minutes; NR: not reached.

Figure 3.

Survival outcomes with idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma based on fludarabine dose reduction. PFS: progression-free survival; CI: confidence interval; OS: overall survival; NR: not reached.