Current evidence and strategies for bridging therapy in CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory large B-cell lymphomas

TL;DR

This review discusses how bridging therapy can help improve outcomes for patients receiving CAR T-cell therapy for aggressive B-cell lymphomas.

Contribution

The paper systematically examines current bridging therapy strategies and highlights unresolved questions to guide future clinical practice.

Findings

Bridging therapy prevents disease progression and may enhance CAR T-cell efficacy.

Chemotherapy, targeted agents, and radiotherapy are commonly used bridging therapy strategies.

Optimal use of bispecific antibodies and Bruton’s tyrosine kinase inhibitors remains unclear.

Abstract

CD19-directed chimeric antigen receptor T-cell (CAR T-cell) therapy has markedly improved the prognosis of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). However, disease progression during the manufacturing period remains a major barrier to successful treatment. Bridging therapy (BT), defined as anti-lymphoma treatment administered between leukapheresis and lymphodepleting chemotherapy, serves two primary purposes: to prevent disease progression ensuring eligibility for CAR T-cell infusion, and to modulate the immune microenvironment to potentially enhance CAR T-cell efficacy or mitigate its toxicity. This review provides a comprehensive overview of current strategies and clinical evidence regarding BT in the context of CAR T-cell therapy. We systematically examine the efficacy and safety profiles of various BT strategies, including chemotherapy, targeted or immunotherapy agents, and radiotherapy. Furthermore, we summarize and compare findings from pivotal clinical trials and real-world studies, offering insights into the practical application and outcomes of BT in diverse clinical settings. Unresolved questions remain, including the optimal implementation of bispecific antibodies as BT regimens, the timing and duration of Bruton’s tyrosine kinase inhibitors administration, the safety and efficacy of reusing polatuzumab vedotin in previously exposed patients, and the standardization of radiotherapy protocols. In conclusion, the rational selection and application of BT strategies hold promise for improving the clinical outcomes of R/R LBCL patients undergoing CAR T-cell therapy.