Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma

PET/CT plays an important role in staging of multiple myeloma (MM) and detecting extramedullary disease (EMD); however, its role in patients treated with commercially available CAR T cell therapies is unclear. We evaluated 61 patients treated with CAR T cell products. In 53 patients, PET/CT was available before CAR T infusion, and 43 had follow-up PET/CT on day 30. Findings from PET/CT were correlated to (CAR) T single-cell dynamics, fitness and T cell receptor diversity after infusion, and serological markers of tumor burden and inflammation. Patients with bone-independent EMD had inferior median progression-free survival (PFS: 3 vs. 15 months, p = 0.01). Univariate and multivariate analysis showed that EMD but not the number of lesions or metabolic tumor volume (MTV) were associated with inferior PFS. High MTV was connected to higher baseline sBCMA and Interleukin-6 levels, but not associated with hampered CAR T cell expansion or decreased fitness of the bystander T cell compartment. Follow-up PET/CTs identified patients with metabolic complete remissions, which were associated with better PFS. PET/CT identifies patients with high risk of relapse after CAR T cell therapy.