1. Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.
- Author
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Frame, David G., Geer, Marcus, Kasha, Salena, Markstrom, Denise, Scappaticci, Gianni, Feeney, Tate, Hayduk, Andrew, Mansoor, Hilary M., Oberfeld, Avery, D'Antonio, Hannah, Anand, Sarah, Sung Won Choi, Maciejewski, John, Pawarode, Attaphol, Riwes, Mary Mansour, Tewari, Muneesh, Magenau, John, and Ghosh, Monalisa
- Subjects
NON-Hodgkin's lymphoma ,T cells ,CD19 antigen ,CYTOKINE release syndrome ,ELECTRONIC health records - Abstract
Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m² and cyclophosphamide 500 mg/m² for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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