{Reference Type}: Journal Article
{Title}: Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.
{Author}: Frame DG;Geer M;Kasha S;Markstrom D;Scappaticci G;Feeney T;Hayduk A;Mansoor HM;Oberfeld A;D'Antonio H;Anand S;Choi SW;Maciejewski J;Pawarode A;Riwes MM;Tewari M;Magenau J;Ghosh M;
{Journal}: Front Immunol
{Volume}: 15
{Issue}: 0
{Year}: 2024
{Factor}: 8.786
{DOI}: 10.3389/fimmu.2024.1403145
{Abstract}: <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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).<BR><B>UNASSIGNED: </B>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.