Alaa Ali, MD, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, discusses findings from a real-world study that compared fludarabine- and bendamustine-based lymphodepletion prior to CAR-T therapy for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). 

The study showed that patients receiving fludarabine-based lymphodepletion had a higher overall response rate but similar complete response without a significant impact on either progression-free or overall survival compared to those receiving bendamustine. However, bendamustine was associated with a reduced incidence of severe cytokine release syndrome, ICANS, and prolonged cytopenia.

Based on these findings, Dr Ali noted that although fludarabine-cyclophosphamide remains the standard of care for lymphodepletion prior to CAR-T therapy, bendamustine-based lymphodepletion is a viable option, especially for those patients at higher risk for treatment-related toxicities.

Dr Ali presented these findings at the 66^th ASH Annual Meeting in San Diego, California.

Transcript:

Hello, my name is Alaa Ali, I'm one of the physicians at the Stem Cell Transplant and Cellular Immunotherapy program at MedStar Georgetown University Hospital. At this year's ASH annual meeting I will be presenting our real-world data on the comparison between fludarabine-based lymphodepletion and bendamustine-based lymphodepletion for CD19 targeting CAR-T cell therapy.

Lymphodepletion it is important for the CAR T-cell persistence and clinical activities. Fludarabine cyclophosphamide is the most commonly used local depletion regimen but a fludarabine shortage in 2022 led to the adoption of alternative regimens like bendamustine however there is limited real world data comparing these two regimens together and to address that we utilize these CMTR database to compare fludarabine-based and bendamustine-based lymphodepletion before CAR T-cell therapy.

What we found is that we identified 5256 patients, so this is a large sample study. When we compared the two groups in terms of response rates and survival outcomes, we found that overall response rate was higher in the fludarabine group compared with the bendamustine group and that was confirmed in multivariate analysis. However, in terms of complete remission response rate, there was no difference in the multivariate analysis between the 2 groups although there was a trend toward lower rates of complete response in the in bendamustine group.

In terms of survival outcomes there was no difference between the 2 groups in terms of progression free survival or overall survival however the main difference between the 2 groups was in terms of safety profile where there was a lower rate of any grade CRS, severe CRS, lower grades of ICANS or neurotoxicity, severe ICANS as well as prolonged cytopenia in the bendamustine group compared to the fludarabine-based lymphodepletion group.

The main take away of this study was that although fludarabine cyclophosphamide remains the standard of care for CAR T-cell therapy as a lymphodepletion regimen, bendamustine is a viable option especially for those who are at high risk for treatment-related toxicities, such as patients with comorbidities or elderly patients who may be at higher risk for toxicities such as neurotoxicity. In those patients bendamustine is a viable option to try to mitigate those toxicities in this group of patients.
 

Source:

Ali A, Ahmed N, Kim S, et al. Real World Comparison of Efficacy and Safety of Fludarabine-Versus Bendamustine-Based Lymphodepleting Chemotherapy for CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy in Relapse/Refractory (r/r) Large B-Cell Lymphoma (LBCL). Presented at the 66^th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, California. Abstract 71.