Phase 1 Dose Escalation Study of Pembrolizumab in Combination with Rituximab and Lenalidomide for Relapsed/Refractory Large B-Cell or Follicular Lymphoma Following Progression after Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy

Introduction:While autologous CD19-targeting chimeric antigen receptor T-cells (CAR T) can induce high complete response (CR) rates in relapsed and refractory (r/r) large B-cell lymphoma (LBCL) and follicular lymphoma (FL), over 50% of patients experience progressive disease. Survival following CAR T failure is dismal, with only 1 in 5 patients living >2 years. Multiple studies indicated that resistance to CAR T therapy may be driven by CAR T cell intrinsic and/or tumor intrinsic mechanisms. Here, we evaluated the combination of PD-1 blockade with rituximab (R) and lenalidomide (len) with the rationale that it would restore the function of exhausted T cells, enhance CAR T function with len and target the tumor and its immunosuppressive microenvironment.