KEY TAKEAWAYS
- The study aimed to assess the safety and efficacy of bendamustine before axi-cel therapy in pts with R/R LBCL.
- Researchers found bendamustine safe and effective as a substitute for lymphodepletion conditioning with less toxicity and improved immune reconstitution.
The combination of fludarabine and cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). The shortage of fludarabine in 2022 made it necessary to explore the alternative regimens with many centers employing single-agent bendamustine as lymphodepletion irrespective of its lack of concerned clinical safety and efficacy data.
Sushma Bharadwaj and the team aimed to evaluate bendamustine’s safety, efficacy, and expansion kinetics as lymphodepletion before axicabtagene ciloleucel (axi-cel) therapy in patients (pts) with relapsed or refractory large B-cell lymphoma (R/R LBCL).
Researchers at Stanford University conducted a study involving 84 consecutive pts with R/R LBCL treated with axi-cel under a uniform toxicity management plan. Among them, 27 pts received alternative lymphodepletion with bendamustine, while 57 received FC.
Results revealed that the best complete response rates were similar between the FC and bendamustine cohorts, with 73.7% and 74%, respectively (P=0.28). There was no significant difference in 12-month progression-free survival (PFS) or overall survival (OS) estimates (P=0.17 and P=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was also similar between the 2 groups.
However, the bendamustine cohort experienced lower proportions of hematological toxicities and required less antibiotic use for neutropenic fever. As measured by quantitative assessment of cellular immunity, immune reconstitution was better in the bendamustine cohort than the FC cohort. CAR T expansion, measured by peak expansion and area under the curve for expansion, was comparable between the two cohorts.
The study concluded that bendamustine is a safe and effective substitute for lymphodepletion conditioning for axi-cel with less hematological toxicity and favorable immune reconstitution in pts with R/R LBCL.
This study was funded by Biostatistics Shared Resource (BSR) of the NIH-funded Stanford Cancer Institute (P30CA124435).
Source: https://pubmed.ncbi.nlm.nih.gov/38955420/
Bharadwaj S, Lau E, Hamilton MP, et al. (2024) “Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma.” J Immunother Cancer. 2024 Jul 1;12(7):e008975. doi: 10.1136/jitc-2024-008975. PMID: 38955420.
