Extramedullary disease but not paraskeletal disease portends inferior outcomes after CAR T cell therapy in multiple myeloma.

Chimeric antigen receptor (CAR) T cell therapy is effective for multiple myeloma (MM), yet patients with plasmacytomas, either paraskeletal disease (PSD) or extramedullary disease (EMD), have poorer outcomes. To better distinguish the effects of EMD and PSD on outcomes, we conducted a single-center, retrospective study of 134 relapsed/refractory MM patients treated with CAR T cells. With a median follow-up of 30.2 months, patients with EMD (n = 34) had significantly worse progression-free survival (PFS) and overall survival (OS) than those with bone marrow-only disease (n = 75): PFS was 24.2 months vs. 9.0 months (HR 2.15, 95% CI 1.31-3.54), and OS was not reached vs. 24.0 months (HR 3.79, 95% CI 1.81-7.94). In contrast, patients with PSD did not experience significantly shorter PFS or OS. Among patients with EMD, those with high extramedullary tumor burden had a lower overall response rate (ORR). For extramedullary tumor burden <25 cm, 25-50 cm, and >50 cm, ORR was 81.0% (66.7% complete response, CR), 83.3% (50% CR), and 57.1% (0% CR), respectively. Importantly, EMD-positive relapses post-CAR T cell therapy comprised half of all relapses observed. In summary, our findings indicate that EMD, but not PSD, is strongly associated with poor outcomes with CAR T cell therapy.