ASH 2024 | Fludarabine versus bendamustine-based lymphodepletion for CAR T-cell therapy in LBCL

Yeah, at this year’s ASH meeting, I’m presenting a real-world experience comparing fludarabine-based lymphodepletion with bendamustine-based lymphodepletion in a large cohort of patients using the CIBMTR database. As we know, lymphodepletion is important for the function of CAR T-cells, critical for the persistence and clinical activity of those cells. Historically, the most commonly utilized lymphodepletion regimen is fludarabine-based lymphodepletion, such as Flu/Cy. But in 2022, there was a shortage, a national fludarabine shortage that led institutions to search for a substitute for fludarabine-based lymphodepletion. And that’s when bendamustine became one of the substitutes. So we went back and looked at all the patients who received fludarabine-based lymphodepletion and bendamustine-based lymphodepletion in the registry. We identified 5,256 patients and we stratified those patients with large B-cell lymphoma that received CAR T-cell therapy. Then we stratified those patients to those who received fluidarabine-based and bendamustine-based lymphodepletion, and then we compared the response rates based on the lymphodepletion regimen. What we found is that the overall response rate is lower in bendamustine-based lymphodepletion compared to fludarabine-based lymphodepletion. The rates of complete response were also lower in the bendamustine group compared to the fludarabine group, but in the multivariate analysis, there was a trend towards lower rates but that difference was not statistically significant. In terms of survival data, we did not find any difference in terms of progression-free survival or overall survival between the two groups. The major difference was in terms of safety profile when the bendamustine group experienced significantly lower rates of any grade ICANS, any severe ICANS, any grade CRS, severe CRS, and prolonged cytopenia. So that was significantly lower in the bendamustine group. So the takeaway, then we did a subset analysis where we looked at only patients who received CAR T-cell infusion between 2021 and 2023 because this is the duration when bendamustine use increased due to the fludarabine shortage. And in this subset, the outcomes were pretty similar to the main cohort. So the main takeaway of this study is that although fludarabine-based lymphodepletion is still the standard of care, bendamustine lymphodepletion is a viable option, especially for those patients at high risk for treatment-related toxicities such as elderly patients or patients with comorbidities.

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