An Externally Controlled Trial to Indirectly Compare Tazemetostat Plus Lenalidomide and Rituximab Versus Lenalidomide and Rituximab after at Least One Prior Systemic Therapy in Patients with Refractory and Relapsed Follicular Lymphoma

BACKGROUND: Follicular lymphoma (FL) is an indolent, incurable lymphoma with a heterogeneous clinical course characterized by multiple relapses. Recent data indicate a potential synergism between tazemetostat and lenalidomide and an additive effect with rituximab, offering a clinical rationale for this as a combination strategy (Batlevi, Blood 2022). SYMPHONY-1 Phase 1b, Stage 1 (EZH-302; NCT04224493) is an open-label, single-arm, safety run-in trial to evaluate the safety and tolerability of tazemetostat combined with lenalidomide plus rituximab (R2). This study indirectly compares the efficacy results of the SYMPHONY-1 Phase 1b single arm trial with an external control arm (ECA) derived from the Flatiron Health Research Database (FHRD), consisting of real-world FL patients treated with R2 after receiving ≥1 prior systemic therapy.