Extramedullary diseasein multiple myeloma is associated with significantly higher rates of severe toxicity following B-cell maturation antigen-targeted CAR T-cell therapy, according to a new paper published in Haematologica.
The retrospective study evaluated the impact of active EMD on toxicity, efficacy, and survival in 108 patients with MM treated with idecabtagene vicleucel (ide-cel; n=32) or ciltacabtagene autoleucel (cilta-cel; n=76). Among the 108 patients, 26 (24%) had EMD, defined as the presence of soft tissue masses in extraosseous locations.
Patients with EMD experienced higher rates of grade 1+ (38% vs 17%; P=0.022) and grade 3+ immune effector cell-associated neurotoxicity syndrome (19% vs 1.2%; P=0.003), as well as grade 1+ (96% vs 78%; P=0.041) and grade 3+ early immune effector cell-associated hematoxicity (31% vs 0; P<0.001).
Nearly all patients with EMD developed severe neutropenia (96% vs 78%; P=0.039). Patients with EMD also 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 nonrelapse mortality (21% vs 2.5%; P=0.003).
“Our study demonstrates that patients with MM who have EMD experience significantly higher rates of severe toxicity following BCMA-targeted CAR-T therapy,” the authors wrote.
“The clinical consequences of this heightened toxicity burden are significant,” the authors noted. “Prolonged neutropenia in patients with EMD led to an increased infection risk, with higher rates of bacteremia and greater use of broad-spectrum antibiotics. The severity of cytopenias further compounded these challenges, increasing the need for red blood cell and platelet transfusions to support hematologic recovery.”
Reference
Portuguese AJ, Liang EC, Huang JJ, et al. Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma. Haematologica. 2025;110(12):3065-3077. doi:10.3324/haematol.2025.287985
