CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting

CAR-T therapy is rapidly reshaping the treatment paradigm of multiple myeloma (MM). At the 2025 ASH Annual Meeting, pivotal trials demonstrated marked efficacy across both relapsed/refractory and newly diagnosed settings. In KarMMa-3, a subgroup analysis of older patients (≥ 70 years) showed idecabtagene vicleucel significantly improved outcomes versus standard care: overall response rate (ORR) 81.6% vs. 48.1%, median progression-free survival (PFS) 18.9 vs. 5.7 months, with median overall survival (OS) not reached in either arm. CARTITUDE-4 showed superior 30-month PFS (71.0% vs. 43.2%), while iMMagine-1 reported an ORR of 97% with 93% minimal residual disease negativity. Notably, frontline CAR-T studies achieved unprecedented outcomes, including 100% ORR, stringent complete response rates approaching 94-97%, and 30-month PFS and OS rates of 88-92%. Together, these data support a paradigm shift toward earlier integration of CAR-T therapy in MM management.