Relapsed or refractory large B‐cell lymphoma after chimeric antigen receptor T‐cell therapy: Current challenges and therapeutic options

Summary Chimeric antigen receptor (CAR) T‐cell (CAR‐T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR‐T therapy have poor outcomes. Multiple mechanisms of CAR‐T therapy failure have been proposed but management of these patients remains a challenge. As CAR‐T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR‐T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody–drug conjugates and next‐generation CAR‐T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR‐T therapy and provide a framework for the ideal sequencing of these novel agents.