Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma.

Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T therapy, yet its impact on treatment-related toxicity remains unclear. This study evaluates the impact of active EMD on toxicity, efficacy, and survival in patients with MM treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). We conducted a retrospective cohort study of all patients with MM who received ide-cel (N=32) or cilta-cel (N=76) as standard-of-care therapy at our institution from August 2021 to October 2024. EMD was defined as the presence of soft tissue masses in extraosseous locations, and outcomes were compared based on EMD status. Among 108 patients, 26 (24%) had EMD. Patients with EMD experienced higher rates of grade (G)1+ (38% vs. 17%; P=0.022) and G3+ immune effector cell-associated neurotoxicity syndrome (19% vs. 1.2%; P=0.003), as well as G1+ (96% vs. 78%; P=0.041) and G3+ early immune effector cell-associated hematoxicity (31% vs. 0; P<0.001). Patients with EMD had more prolonged severe neutropenia (median: 7 vs. 2 days; P<0.001), greater cefepime use (median 10 vs. 6 doses; P=0.039), and higher rates of bacteremia (15% vs. 2.4%; P=0.029). In terms of efficacy, patients with EMD had lower complete response rates (20% vs. 59%; P<0.001), shorter median progression-free survival (7.6 vs. 24.6 months; P<0.001), and shorter median overall survival (20 months vs. not reached; P<0.001; 1-year estimates, 53% vs. 96%) and higher 1-year non-relapse mortality (21% vs. 2.5%; P=0.003). EMD is associated with increased toxicity, delayed hematologic recovery, more infectious complications, and reduced survival in patients with MM receiving CAR T therapy.