Bendamustine Demonstrates Safety, Efficacy for Lymphodepletion Before Tisagenlecleucel in R/R Large B-Cell Lymphoma

Bendamustine is an effective lymphodepletion regimen before tisagenlecleucel in patients with refractory/relapsed large B-cell lymphomas, according to findings from a recent study published in The Annals of Oncology.

“Anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T) is now a standard treatment of relapsed or refractory B-cell non-Hodgkin lymphomas; however, a significant portion of patients do not respond to CAR-T and/or experience toxicities,” wrote Guido Ghilardi MD, University of Pennsylvania, Philadelphia, PA, and colleagues, “Lymphodepleting chemotherapy is a critical component of CAR-T that enhances CAR-T-cell engraftment, expansion, cytotoxicity, and persistence.”

In this study, the researchers compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n = 42) or bendamustine (n = 90) before tisagenlecleucel in 2 groups of patients with relapsed/refractory large B-cell lymphomas treated consecutively at 3 academic institutions in the United States and Europe.

The efficacy of tisagenlecleucel was similar between the 2 groups, but fludarabine/cyclophosphamide led to more profound lymphocytopenia after tisagenlecleucel infusion, compared with bendamustine. Bendamustine-treated patients had higher nadir neutrophil counts, hemoglobin levels, and platelet counts, as well as a shorter time to blood count recovery, and received fewer platelet and red cell transfusions. They also noted fewer episodes of infection, neutropenic fever, and post-infusion hospitalization in the bendamustine cohort compared with patients receiving fludarabine/cyclophosphamide.

There were significant differences in the frequency and severity of adverse events. In particular, patients treated with bendamustine had lower rates of cytokine release syndrome and neurotoxicity. There were also higher rates of hematological toxicities observed in patients treated with fludarabine/cyclophosphamide.

“Bendamustine for lymphodepletion before tisagenlecleucel has efficacy similar to fludarabine/cyclophosphamide, with reduced toxicities,” Dr Ghilardi and colleagues concluded.

Source:

Ghilardi G, Chong EA, Svoboda J, et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Annals Oncol. 2022;33(9):916-928. doi:10.1016/j.annonc.2022.05.521