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885 Outcome of Relapsed/Refractory Aggressive B-Cell Lymphoma Patients Relapsing after Anti-CD19 CAR T-Cells and Enrolled in the Descar-T French National Registry

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Real World evidence for CAR-T Management II
Hematology Disease Topics & Pathways:
Biological, Lymphomas, Non-Hodgkin Lymphoma, B Cell Lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Aggressive Lymphoma, Therapies, Lymphoid Malignancies
Monday, December 13, 2021: 6:45 PM

Roberta Di Blasi, MD, PhD1*, Steven Le Gouill, MD, PhD2*, Emmanuel Bachy, MD, PhD3*, Guillaume Cartron, MD, PhD4*, David Beauvais, MD5*, Fabien Le Bras6*, Francois Xavier Gros, MD7*, Sylvain Choquet8*, Pierre Bories9*, Pierre Feugier, MD, PhD10*, Rene-Olivier Casasnovas, MD11*, Jacques-Olivier Bay, MD, PhD12, Mohamad Mohty, MD, PhD13, Magalie Joris, MD14*, Thomas Gastinne, MD15*, Pierre Sesques, MD16*, Jean Jacques Tudesq, MD17*, Laetitia Vercellino18*, Franck Morschhauser, MD, PhD19*, Elodie Gat20*, Florence Broussais21*, Roch Houot, MD, PhD22* and Catherine Thieblemont, MD23

1Department of Hematology, Assistance Publique Hôpitaux de Paris - Hopital Saint-Louis, University of Paris, Paris, France
2CHU de Nantes—Hotel Dieu, Nantes, France
3Department of Hematology, Lyon-Sud Hospital, Pierre-Benite, France
4Département d'Hématologie clinique, CHU de Montpellier, Montpellier, France
5Hématologie clinique, CHU de Lille, Lille, France
6Unité hémopathies Lymphoïdes, Creteil Cedex, France
7Hématologie Clinique et Thérapie cellulaire, CHU Bordeaux, Merignac, France
8La Pitie Salpetriere Hospital, APHP-Sorbonne Universite, Paris, France
9Hematology, Oncopole Toulouse, Toulouse, FRA
10Département d'Hématologie, CHRU Nancy, Hôpitaux de Brabois, Vandoeuvre-lès-Nancy, France
11Department of Hematology, CHU Dijon, Dijon, France
12CHU de Clermont-Ferrand, Site Estaing, Service de thérapie cellulaire et d'hématologie clinique adulte, Clermont-Ferrand, France
13Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Paris, France
14Hematology department, CHU Amiens, Amiens, France
15Clinical Hematology, University Hospital of Nantes,, Nantes Cedex 1, France
16Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Benite, France
17Hematology Department, Montpellier University Hospital, Montpellier, France, Montpellier, France
18APHP, Hôpital Saint Louis, Nuclear Medecine, Paris, France
19Hematology Department, Lille University Hospital, Lille, France
20Institut Carnot CALYM, PIERRE-BENITE, FRA
21LYSARC, Lyon, France
22University Hospital of Rennes, Rennes, FRA
23APHP, Hôpital Saint-Louis, Hemato-Oncology; Paris University, Paris, France

Background. Anti-CD19 Chimeric Antigen Receptor (CAR) T-cells are a major therapeutic advance in the management of patients (pts) with relapsed/refractory aggressive B-cell lymphoma (R/R aggressive BCL) with reported overall response rates between 40% and 83% in the pivotal trials (ZUMA1, JULIET, TRANSCEND) as well as in the real-life cohorts with either axicabtagene ciloleucel (axi-cel, Yescarta) or tisagenlecleucel (tisa-cel, Kymriah). However, a significant number of pts will experience progression or relapse after infusion with an estimated 24-month progression-free survival (PFS) of between 33% and 42%. DESCAR-T is a nationwide registry that aims to collect real-life data for all pts treated with commercialized CAR T-cells in France. It represents a unique opportunity to investigate the outcome of pts who relapse after CAR T-cell therapy.

Patients and Methods. In all, 680 pts with R/R aggressive BCL were registered in DESCAR-T from August 2018 and 550 were infused at the time of the present analysis (April 12, 2021) with either axi-cel (n=350) or tisa-cel, n=200). All pts gave informed informed consent before DESCAR-T registration. Progression and relapse after CAR T-cells were defined based on the Cheson 2014 response assessment criteria.

Results. With a median follow-up (F-up) of 7.9 months, 238 pts (43.3%) out of 550 treated pts relapsed, after axi-cel in 136 pts (F-up = 9.0 months [5.1 – 9.7]) and after tisa-cel in 102 pts (F-up = 7.8 months [5.9 – 10.4]). Histological subtypes were DLBCL (n 178, 74.8%), PMBL (n=11, 4.6%), HGBCL (n= 3, 1.3%), transformed follicular lymphoma (tr FL) (n=31, 13%), or other histologies (FL n=2, PCNSL n=1, tr MZL n=3, unclassifiable hodgkin/DLBCL n=9). At time of registration, median age was 62 years (range 18;77), 43.6% were aged >65 yrs, and 67.2% were male; 184 (79.7%) presented with advanced disease (stage III or IV), and 13 (5.9%) with low age-adjusted International Prognostic Index (aaIPI), 82 (37.1%) with low-intermediate aaIPI, 110 (49.8%) with high-intermediate aaIPI, and 16 (7.2%) with high aaIPI. At time of CAR T-cell infusion, 36 (18.9%) pts presented with ECOG PS >=2 and 72 (38.9%) with an elevated LDH level. The median number of lines prior to CAR T-cell infusion was 3 (range 2-9), including 48 (20.1%) transplant (46 auto-HSCT and 2 allo-HSCT). Median time between order and infusion was 50 days (IQR 43; 59). Bridging therapy was administered to 87.8% of the pts, with a high-dose regimen including combined immunochemotherapy for 84.5% of the pts. Failure after CAR T-cells occurred after a median time of 2.71 months (range 0.2; 21.5), 54 (22.7%) being during the first month after infusion (< M1) and 156 (65.5%) during the first-three months after infusion (<M3). At failure, 154 (64%) patients received treatments that maybe combined and described as followed : 70 (45.5%) lenalidomide, 70 (45.5%) various immunotherapies (rituximab, daratumomab, polatuzumab), 31 (20.1%) a combined immunochemotherapy with various regimens (R-DHAX, RICE, Pola-R-Benda,...), 21 (13.6%) an anti-PD1 immune checkpoint inhibitor (Nivolumab, pembrolizumab), 11 (7.1%) bi-specific T-cell engagers (TCE), 18 (11.7%) radiotherapy, and 3 a transplant (1 an auto-HSCT and 2 an allo-HSCT). The overall response rate to the salvage therapy after CAR T-cells was 11% (complete response rate 5.2%). The median PFS was 2.8 months (95% CL, 2.4 -3.1). The median overall survival (OS) was 5.2 months (95% CL, 4.1- 6.6) (Figure 1A). The median OS was even shorter in pts who failed during the first month (1.9 months [95% CL, 1.1- 3.2] vs 6.7 months [95 CL 5.5 : 9.3] p<0.0001) (Figure 1B). 26.9% of the pts in the overall cohort were alive at 6 months, but only 18.9% were alive in the group of pts relapsing during the first month. In multivariate analysis, predictors of OS were high LDH level at time of infusion, time to failure < 1 month after CAR T-cells, no access to immuno-oncology treatment such as TCE or lenalidomide.

Conclusion. This study is the first analysis reporting the outcome of patients with R/R aggressive BCL relapsing after anti-CD19 CAR T-cells. These results demonstrate the poor outcome of these pts and identifies the need for further innovative treatment strategies.

Figure1. Overall survival from the CAR T-cell infusion in patients with R/R LBCL relapsing after CAR T-cells. (A) overall population. (B) according to the interval between CAR T-infusion and relapse (< 1 month and > 1 month)

Disclosures: Di Blasi: Novartis: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Bachy: Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Honoraria. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Le Bras: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. 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. Mohty: Amgen: Honoraria; Jazz: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria. Gastinne: Gilead/kyte: Honoraria; Takeda: Honoraria. Sesques: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Chugai: Honoraria. Morschhauser: Bristol-Myers Squibb: Consultancy, 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; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Genentech, Inc.: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy.

*signifies non-member of ASH