CD19 CAR T-Cell Therapy in Patients with Relapse/Refractory DLBCL: Retrospective Analysis of the Eligibility Criteria

Autor: Driss Chaoui, Vincent Camus, Jean-Pierre Marolleau, Maxime Berquier, Véronique Meignin, Géraldine Salmeron, Bénédicte Deau-Fischer, Rene-Olivier Casasnovas, Luc Mathieu Fornecker, Anne Quinquenel, Celia Salanoubat, Frédérique Kuhnowski, Véronique Morel, Gandhi Damaj, Roberta Di Blasi, Pierre Feugier, Catherine Thieblemont, Sophie Bernard, Elie Azoulay, Michael Darmon, Jérôme Paillassa, Guillaume Cartron, Sophie Rigaudeau, David Sibon, Emmanuel Gyan, Vincent Delwail, Sylvie Chevret, Corinne Haioun, Jean Valère Malfuson
Přispěvatelé: Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Fondation FondaMental [Créteil], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, Argenteuil, Centre Hospitalier Victor Dupouy, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie [Institut Curie], Institut Curie [Paris], Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Service clinique des Maladies du Sang, CHU Amiens-Picardie, Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique [CHU Reims], Hôpital universitaire Robert Debré [Reims], Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Sud Francilien, Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DESSAIVRE, Louise
Rok vydání: 2019
Předmět:
Zdroj: Blood
Blood, 2019, 134 (1), ⟨10.1182/blood-2019-129532⟩
ISSN: 1528-0020
0006-4971
Popis: Introduction: The autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells demonstrated significant clinical benefits and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with an ORR of 52-83% and CR of 40-58% in the 3 pivotal clinical trials (ZUMA-1, TRANSCEND-NHL-001, JULIET), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. The CD19 CAR T-cells Axicabtagene and Tisagenlecleucel have been approved in France since June 2018 for patients with DLBCL, primary mediastinal B-cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after > 2 systemic therapy lines. However, all patients are not deemed eligible for such therapy. Here we describe the characteristics of the non-eligible patients and the causes of non-eligibility for CD19 CAR T-cells at our center. Methods: We performed a retrospective analysis of all patients for whom our center was contacted for potential eligibility to CD19 CAR T-cells. Upon each request, a screening form was completed by the referring hospital to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to > 2 systemic therapy lines) and the absence of contra-indications (CNS involvement (MRI mandatory), active infection). The patient was then evaluated in our hospital to check the predetermined eligibility criteria: age, comorbidities, LVEF > 45%, no pericarditis or cardiogram abnormality, creatinine clearance > 60 mL/min, ALT/AST < 2.5 N, total bilirubin < 1.5 mg/dL, no pleural effusion, SpO2 > 92% without oxygen, lymphocytes > 100/µL, no rapid progressive disease (compressive mass, PS > 2 or rapid increase of LDH), or no active neurological/auto-immune disease. In case of severe comorbidities or age> 70, patient's frailty index was assessed by an ICU physician. Eligibility was then finally validated by our local board through a careful case-by-case analysis. Results: Between June 2018 and July 31, 2019, 221 requests were analyzed. Evaluation is still ongoing for 6 patients (3%). 80/215 patients (37%) were deemed eligible for CAR T-cells, 58 patients (27%) were excluded before any visit at the expert hospital because of histology other than DLBCL, PMBL and tFL (n=30: non-transformed FL 9, transformed SLL/CLL 7, transformed Waldenström 3, transformed MZL 3, MZL 2, primary CNS lymphoma 2, SLL/CLL 1, HL 1, lymphoblastic lymphoma 1, CD19- 1), < 2 previous lines (n=7), CNS involvement (n=7), administrative reason (n=14). The remaining 77 patients (36%) were deemed non-eligible for CAR T-cells after the first visit. Median age was 59 years (range 18-86, 41% ≥ 65 years), 68% were male. There were 62, 4 and 2 patients with DLBCL, PMBL and tFL, respectively. Median number of prior lines was 3 (range 2-11, 43% > 3 lines), 86% of patients presented with a primary refractory disease. Nine patients were with a refractory disease despite stem cell transplantation (SCT, 5 autologous, 3 allogeneic and 1 both). Considering these 77 patients, 12 (16%) had 2 concomitant causes of non-eligibility. Overall, the two main causes of non-eligibility were rapid disease progression (n=49) and major frailty (n=23), including 10 patients with 11 severe organ dysfunctions [5 cardiac, 3 kidney, 1 liver, 1 respiratory and 1 heavy engine handicap]. Replicative viral infections (n=4) constituted also an important cause of frailty: HIV (1), HBV (2), HBV + HCV (1). Two patients had a solid organ transplantation requiring immunosuppressive drugs. Advanced neurological diseases (n=4) included: extrapyramidal syndrome (3), advanced multiple sclerosis (1). Active autoimmune diseases were a cause of frailty for 2 patients: thyroiditis (1), periodic fever (1). In one patient, the screening evaluation showed a concomitant malignancy. Other causes of non-eligibility were found in 17 patients: complete remission after the salvage therapy (n=7), age > 80 (n=4), severe thrombocytopenia < 20 G/L (n=2), no slot available (n=1), patient refusal (n=3). Outcomes of the non-eligible patients (alternative treatments, survival) will be presented at the meeting. Conclusion: In this pioneering experience, 37% of patients in whom a CAR T-cell request is made are ultimately deemed eligible for the therapy. Other patients are either rapidly excluded based on lack of CAR T-cells indications (27%), or deemed non-eligible because of failure to control the disease / major frailty (36%). Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Gyan:Pfizer: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Novartis: Honoraria.
Databáze: OpenAIRE
Externí odkaz: