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743 Kte-X19 in Relapsed or Refractory Mantle-Cell Lymphoma, a “Real-Life” Study from the Descar-T Registry and Lysa Group

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Cellular Therapies for Low and High Grade Lymphomas
Hematology Disease Topics & Pathways:
Lymphomas, Non-Hodgkin Lymphoma, Clinical Research, Diseases, Real World Evidence, Registries, Lymphoid Malignancies
Monday, December 13, 2021: 3:45 PM

Charles Herbaux, MD1, Caroline Bret, PhD, PharmD2*, Roberta Di Blasi, MD, PhD3*, Emmanuel Bachy, MD, PhD4*, David Beauvais, MD5*, Elodie Gat6*, Thomas Gastinne, MD7*, Florence Broussais8*, Guillaume Cartron, MD, PhD9*, Alexis Cuffel10*, Loic Ysebaert, MD, PhD11*, Mikael Roussel, MD, PhD12*, Krimo Bouabdallah13*, Julien Guy, MD14*, Arnaud Campidelli15*, François Van Laethem16*, Rene-Olivier Casasnovas, MD17*, Remy Dulery18*, Franck Morschhauser, MD, PhD19*, Sophie Caillat-Zucman, MD, PhD20*, Roch Houot21* and Steven Le Gouill22

1Hematology Department, Montpellier University Hospital, Montpellier, France, Montpellier, France
2University of Montpellier, UFR Medecine, Montpellier, France
3Department of Hematology, Assistance Publique Hôpitaux de Paris - Hopital Saint-Louis, University of Paris, Paris, France
4Department of Hematology, Lyon Sud Hospital, Lyon, France
5Hématologie clinique, CHU de Lille, Lille, France
6Institut Carnot CALYM, PIERRE-BENITE, FRA
7Clinical Hematology, University Hospital of Nantes,, Nantes Cedex 1, France
8LYSARC, Lyon, France
9Département d'Hématologie clinique, CHU de Montpellier, Montpellier, France
10APHP, hôpital Saint-Louis; Immunologie, Paris, France
11Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
12CHU Rennes, Rennes, France
13Department of Hematology and Cell Therapy, University Hospital, Bordeaux, France
14Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Dijon, DIJON, France
15CHU, Nancy, France
16CHU, Montpellier, France
17Department of Hematology, CHU Dijon, Dijon, France
18Saint-Antoine Research Center, Inserm UMR938, Sorbonne Université, Paris, France
19Hematology Department, Lille University Hospital, Lille, France
20Laboratory of Immunology, Saint Louis Hospital, APHP, Paris, France
21CHU, Rennes, FRA
22Service d’hématologie clinique du CHU de Nantes, INSERM CRCINA Nantes-Angers, NeXT Université de Nantes, Nantes, France

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 7th 2020 until data extraction on June 18th 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 (CMAX, Figure C) and time to maximal expansion (TMAX, Figure D) are shown. We observed a statistical trend to a shorter TMAX 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.

Disclosures: Herbaux: F. Hoffmann-La Roche Ltd: Honoraria; AbbVie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Bachy: Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Honoraria. Gastinne: Gilead/kyte: Honoraria; Takeda: Honoraria. 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: Gilead: Other: Travel support and registration fees for scientific meetings ; Takeda: Consultancy; Novartis: Honoraria. Morschhauser: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Genentech, Inc.: Consultancy; 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; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: 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.

*signifies non-member of ASH