B-cell non-Hodgkin lymphomas that have relapsed or become resistant to treatment are often treated using anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T); nonetheless, many patients do not react to CAR-T and/or develop side effects. A crucial element of CAR-T that improves CAR-T-cell engraftment, expansion, cytotoxicity, and durability is lymphodepleting chemotherapy. However, for a study, researchers predicted that the lymphodepletion protocol might compromise the security and effectiveness of CAR-T.
Two cohorts of patients with relapsed or refractory large B-cell lymphomas were treated concurrently at 3 academic institutions in the United States (the University of Pennsylvania, n=90; Oregon Health & Science University, n=35) and Europe (University of Vienna, n=7); they compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n=42) or bendamustine (n=90). The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and, where applicable, the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading were used to evaluate toxicities and evaluate responses in accordance with the Lugano 2014 criteria.
Compared to bendamustine, fludarabine/cyclophosphamide caused more severe lymphocytopenia following tisagenlecleucel infusion, but the effectiveness of tisagenlecleucel was comparable in both groups. The frequency and severity of adverse events did, however, differ significantly. Patients receiving bendamustine exhibited significantly decreased incidence of neurotoxicity and cytokine release syndrome. Patients who received fludarabine/cyclophosphamide also experienced a greater incidence of hematological toxicity. Patients on bendamustine experienced faster blood count recovery times, higher nadir neutrophil, hemoglobin, and platelet count, and required fewer platelet and red blood cell transfusions. When compared to individuals receiving fludarabine/cyclophosphamide, patients in the bendamustine cohort experienced fewer bouts of infection, neutropenic fever, and post-infusion hospitalization.
Bendamustine offered effectiveness comparable to fludarabine/cyclophosphamide for lymphodepletion prior to tisagenlecleucel with decreased toxicities, such as cytokine release syndrome, neurotoxicity, infectious and hematological toxicities, as well as decreased hospital occupancy.