Bendamustine Treatment Before CAR T-Cell Therapy Results in Poorer Outcomes in Patients with LBCL

Study results indicate that patients with refractory large B-cell lymphoma (LBCL) who received chimeric antigen receptor (CAR) T-cell therapy and treatment with bendamustine prior to apheresis had a shorter progression-free survival and overall response rate compared to those who were bendamustine-naïve, regardless of the dose received and the patients’ characteristics. In addition, this study is the first to report on the impact of recent exposure (9 months) to bendamustine as an independent factor of poorer outcomes of CAR T-cell therapy in patients with LBCL, according to the investigators.

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Bendamustine is an alkylating drug, a type of chemotherapy commonly used in the treatment of chronic lymphocytic leukemia, non-Hodgkin lymphoma, and myeloma. In addition, the study authors note that there are clinical consensus guidelines on the limitations of bendamustine usage due to the toxic effect of patient lymphocytes.

“While the advent of CAR T-cell therapy has undoubtedly revolutionized the treatment landscape of patients with relapsed or refractory large B-cell lymphoma, only between 30% and 40% of patients infused with CAR T-cells achieve a durable remission,” said first author Gloria Iacoboni, hematologist at Vall d’Hebron University Hospital (HUVH), clinical investigator of Vall d’Hebron Institute of Oncology (VHIO) experimental hematology group, in a press release.

The retrospective study enrolled 439 patients who had received CAR T-cell therapy either in third or later lines of treatment. Patients were divided into 2 different cohorts based on whether they had been exposed to bendamustine prior to T-lymphocyte apheresis. Approximately 18% of patients (n = 80) in the study had been exposed to bendamustine at a median of 6 months before T-cell collection with a median of 4 cycles of therapy.

Further, the investigators identified that previous exposure as an independent factor was associated with poorer outcomes following CAR T-cell therapy. This conclusion was drawn after the baseline characteristics of patients were statistically equated to rule out the potential influence bendamustine and more aggressive disease had on the results.

“Patients who progress after this therapy have low response rates to salvage regimens and long-term outcomes are dismal. Advancing insights into factors associated with treatment success will ultimately help us to improve outcomes for more of our patients,” said corresponding author Pere Barba, MD, PhD, clinical investigator of VHIO Experimental Hematology Group and director of the advanced therapies program of HUVH’s Hematology Service, in the press release.

In addition, a second analysis confirmed that recent exposure—9 months prior to apheresis—to bendamustine contributed to worse results. Further, recent exposure to bendamustine was associated with poorer outcomes in patients regardless of the dose received or the characteristics of the patients. The 42 patients who had received the agent 9 months prior to apheresis had a median overall survival of 4.6 months compared to those who were in the bendamustine-naïve group (23.5 months).

“On the basis of our results, the use of bendamustine should be avoided when possible in patients with refractory LBCL who are potential candidates for CAR T-cell therapy,” said Barba in the press release. “Our findings should be considered in future clinical guidelines; not only for these lymphomas but also for other types of lymphoma that may eventually progress and require CAR T therapies, as we collectively seek to anticipate all treatment scenarios and improve patient outcomes.”

Reference

Vall D’Hebron Institute of Oncology. Treatment with bendamustine prior to CAR T-cell therapy in patients with refractory large B-cell lymphoma associates with poorer treatment outcomes. News release. December 19, 2023. Accessed January 2, 2024. https://www.eurekalert.org/news-releases/1029438