Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus causing causing Coronavirus disease 2019 (COVID-19) was reported for the first time in Wuhan (Hubei, China) in December 2019 (1, 2) and has become a major public health concern all over the world.…

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Introduction The French health agency granted access to KTE-X19 in its early access program (French ATUs) for patients with relapsed or refractory (R/R) mantle-cell lymphoma (MCL) who failed after at least one line of chemoimmunotherapy and Bruton's tyrosine kinase (BTK) inhibitor. DESCAR-T is the French national registry for all patients treated with CAR-T cells (commercial or early access program). DESCAR-T designed and sponsored by LYSA/LYSARC aims to collect "real-life" data about CAR-T cell eligible patients in all hematological malignancies. We report the first results of "real-life" use of KTE-X19 in R/R MCL. Methods. All patients with MCL and registered in DESCAR-T were eligible for the present study. The data collection started at time of the medical decision to treat with KTE-X19. All patients gave informed consent before DESCAR-T registration. Response was determined by investigators per the Lugano criteria. CAR-T cells were monitored in peripheral blood samples of 14 patients by multiparametric flow cytometry routine procedures, using the biotinylated CD19 CAR detection reagent (Miltenyi Biotec©). Results Our study started at the beginning of the French early access program on January 7 th 2020 until data extraction on June 18 th 2021. A total of 57 patients were registered, including 6 commercial use registrations of KTE-X19 (after the end of early access program). KTE-X19 product has been ordered for 55 patients of whom 47 have been infused with CAR-T cells. KTE-X19 was not ordered in 2 cases because of patient decision. It was not infused in 8 patients because of disease progression (n=3), manufacturing failure (n=3), cardiac disease (n=1) and uncontrolled infection (n=1). At the time of registration in DESCAR-T, median age of infused patients was 67 years (range 45-79), 93.6% of patients were male. Median number of prior lines of treatment was 3 (range 2-8) with 34% of autologous stem cell transplant. Initial Ki67 was high (>30%) in 78.6% of patients, 52.4% of patients had elevated LDH and 21.1% had a poor performance status (PS≥2) at inclusion.Median time between CAR-T order and infusion was 56 days (range 35-134) and 87.2% of patients had a bridging therapy. Median follow-up since CAR-T administration was 3.3 months (range 0-12.6). The best overall response rate for the 42 patients with at least one efficacy evaluation was 88%, including CR in 61.9%. PFS calculated from KTE-X19 infusion at 6 months was 57.9% (Figure A) and median duration of 5.3 months. Cytokine release syndrome (CRS) was observed in 78.7% of patients and a neurotoxicity in 48.9%. Transfer in ICU was needed in 27.7% of patients, with a median duration of hospitalization of 5 days. CRS or neurotoxicity of ≥ grade 3 were seen in 4 patients (8.5%), one patient presented both AEs. Among the 47 infused patients, 5 died, 4 of progressive disease and 1 of grade 5 CRS. Cellular kinetics parameters including area under the curve (AUC) representing the exposure from day 0 to day 28 (Figure B), maximal expansion post infusion (C MAX, Figure C) and time to maximal expansion (T MAX, Figure D) are shown. We observed a statistical trend to a shorter T MAX in responders. Conclusion This first analysis of "real-life" use of KTE-X19 supports results of clinical trials using CAR-T cells in R/R MCL. The safety profile and the overall response rate are also in line with previously published data. Taken together, the present "real-life" study experience supports the use of KTE-X19 in R/R MCL who failed after BTKi. Updated results will be presented at the meeting. Figure 1 Figure 1. Disclosures Herbaux: Abbvie: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria; Takeda: Honoraria, Research Funding. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding. Bouabdallah: Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings . Morschhauser: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Janssen: Honoraria; Genentech, Inc.: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees. Houot: MSD: Honoraria; Gilead: Honoraria; Roche: Honoraria; Bristol-Myers Squibb: Honoraria; Kite: Honoraria; Novartis: Honoraria; Jsnssen: Honoraria; CHU Rennes: Current Employment; Celgene: Honoraria.

The cost and toxicities of chimeric antigen receptor (CAR)-T cells require efforts to identify the patients most likely to respond. We determined whether the quality of T lymphocytes at the time of apheresis influenced the clinical response to commercial tisagenlecleucel (tisa-cel) in 30 large B-cell lymphoma patients. The T-cell phenotype and proliferative capacity were determined by flow cytometry. Clinical efficacy outcome (partial or complete response at 1 and 3 months, progression-free survival (PFS) and overall survival (OS)) was evaluated based on the Lugano criteria. The proportion of naïve/stem cell memory (TN/SCM) correlated with the proliferative potential of CD4 and CD8 T cells, and with the relative expansion of CD4 and CD8 subsets during CAR-T cell manufacture. Early clinical response, PFS and OS were positively associated with higher proportions of CD8 TN/SCM and higher CD8 T-cell proliferative potential, while CD4 T cells had opposite effects. In multivariate analysis, CD8 TN/SCM proportion and International Prognostic Index (IPI) at the time of apheresis were independent risk factors for early progression. Our data show that an easy characterization by flow cytometry of the T-cell phenotype at the time of decision to use commercial CAR-T cells can help to better select patients who will respond.