-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2412 Immunological Cytopenias Induced By Anti-Programmed Cell Death (ligand) 1 AntibodiesClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster II
Hematology Disease Topics & Pathways:
Biological, autoimmune disorders, Diseases, Non-Biological, Therapies, checkpoint inhibitors, Immune Disorders, Clinically relevant, Quality Improvement
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Jean-Marie Michot, MD1*, Nicolas Delanoy2*, Thibault Comont3*, Nora Kramkimel4*, Romain Dupont5*, Julien Lazarovici, MD6*, Stéphane Champiat1*, Caroline Robert2*, Charles Herbaux, MD7*, Benjamin Besse2*, Claude Chahine, MD8*, Aude Guillemin4*, Christine Mateus2*, Patricia Pautier2*, Philippe Saiag4*, Emmanuela Madonna2*, Marie Maerevoet, MD9*, Jean-Christophe Bout10*, Charlotte Leduc11*, Pascal Biscay12*, Gilles Quere13*, Christophe Nardin14*, Mikael Ebbo15*, Laurence Albiges2*, Grégoire Marret4*, Virginie Levrat16*, Cécile Dujon17*, Salim Laghouati2*, Laure Croisille, MD, PhD18*, Anne-Laure Voisin2*, Bertrand Godeau, M.D19*, Christophe Massard1*, Vincent Ribrag, MD20, Aurelien Marabelle, MD, PhD21*, Marc Michel22* and Olivier Lambotte2*

1Gustave Roussy Cancer Campus, Villejuif, France
2Gustave Roussy, Villejuif, France
3Toulouse-oncopole, Toulouse, FRA
4Assistance Publique Hopitaux de Paris, Paris, France
5Oncopole Toulouse, Toulouse, France
6Department of Hematology, Institute Gustave Roussy, Villejuif, France
7Service des Maladies du Sang, CHU Lille, Lille, France
8Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France
9Dpt of Hematology, Institut Jules Bordet, ULB, Brussels, Belgium
10Saint Brieux Hospital, Saint Brieux, France
11Strasbourg Universitary Hospital, Strasbourg, France
12Bordeaux Hospital, Bordeaux, France
13Brest Hospital, Brest, France
14Besancon Hospital, Besancon, France
15Marseille Hospital, Marseille, France
16La Rochelle Hospital, La Rochelle, France
17Versailles Hospital, Versaille, France
18Mondor Hospital, Creteil, France
19Henri Mondor University Hospital, Créteil, France
20DITEP, Gustave Roussy, Université Paris-Saclay, Villejuif, France
21Gustave Roussy, Villejuif, FRA
22Hôpital Henri Mondor, Créteil, France

Background. Anti-programmed death (ligand) 1 (PD-(L)1) antibodies are novel immunotherapies for cancer. Anti-PD(L)1 can induce immune-related adverse events (irAEs), which most frequently affect the skin, endocrine glands, lung, liver and digestive tract, however all organs including the hematopoietic system can potentially be involved. Hematologic irAEs (hem-irAEs) have not yet been extensively characterized. This study based on a pharmacovigilance academic registry aims to provide a comprehensive report of hem-irAEs.

Patients and methods. All grade 2 or higher hem-irAEs recorded in pharmacovigilance databases were recorded in this study over the period 2013–2018. Pharmacovilance database included REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie) and ImmunoTOX committee of Gustave Roussy, and the French nationwide CeReCAI registry (Centre de Référence des Cytopénies Auto-Immunes de l’adulte). Prevalence of hem-irAE was calculated in the prospective REISAMIC registry. The hem-irAE’s severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03).

Results. Thirty-five patients (21 men and 14 women) with hem-irAEs related to anti-PD(L)1s were recorded. The prevalence of grade ≥2 hem-irAEs among patients treated with anti-PD(L)1s was estimated to 0.54%. The patients’ median age was 65 years (range: 30-90), tumor types were melanoma (n=15), non-small-cell lung carcinoma (n=12), lymphoma (n=4), and other types (n=4). A concomitant medical history of chronic lymphocytic leukemia was found in 3 (9%) patients. The hem-irAEs were classified as neutropenia (n=9; 26%), auto-immune hemolytic anemia (n=9; 26%), immune thrombocytopenia (IT) (n=9; 26%), pancytopenia or aplastic anemia (n=5; 14%), bicytopenia (n=2; 6%) and pure-red cell aplasia (n=1; 3%). The maximum grade of severity reported was grade 2 in 3 (9%) patients, grade 3 in 8 (23%) patients and grade 4 in 24 (69%) patients. Two patients (6%) had a poor outcome and died in the course of the hem-irAE. Treatments given for the hem-irAE were steroids in 31 (89%) patients, granulocyte colony-stimulating factor in 13 (37%) patients, intravenous immunoglobulins in 6 (17%) patients and rituximab in 2 (6%) patients. The median time to onset from anti-PD(L)1 initiation was 10.1 weeks (range 0.9 – 198.0). With a median follow-up of 19 (range 2-180) weeks, the rate of resolution of hem-irAE was 67% (78% for IT and 40% for aplastic anemia patients, p=0.524). After resolution, 6/35 (17%) patients were rechallenged and 3 of them (50%) recurred the same hem-irAE.

Conclusion. The clinical spectrum of hematologic irAE is wide and dominated by neutropenia, hemolytic anemia and immune thrombocytopenia. Aplastic anemia is rarer and present as a life-threatening condition. The prevalence of grade ≥2 hematologic irAEs following anti-PD(L)1 was 0.54%. The recurrence rate after rechallenge was 50%. Further prospective investigations are warranted to better detect and manage hematologic immune-related adverse events.

Disclosures: Michot: Novartis: Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; Debiopharm: Other: Principal/sub-Investigator of Clinical Trials ; Kura Oncology: Other: Principal/sub-Investigator of Clinical Trials ; Nektar Therapeutics: Other: Principal/sub-Investigator of Clinical Trials ; Boeringer Ingleheim: Other: Principal/sub-Investigator of Clinical Trials ; Janssen: Honoraria, Other: Principal/sub-Investigator of Clinical Trials ; Menarini: Other: Principal/sub-Investigator of Clinical Trials ; Oncopeptides AB: Other: Principal/sub-Investigator of Clinical Trials ; Eos: Other: Principal/sub-Investigator of Clinical Trials ; Orion: Other: Principal/sub-Investigator of Clinical Trials ; Nanobiotix: Other: Principal/sub-Investigator of Clinical Trials ; Pfizer: Other: Principal/sub-Investigator of Clinical Trials ; Astex: Other: Principal/sub-Investigator of Clinical Trials ; Servier: Other: Principal/sub-Investigator of Clinical Trials ; Eisai: Other: Principal/sub-Investigator of Clinical Trials ; Astra-Zenenca: Honoraria, Other: Principal/sub-Investigator of Clinical Trials & Non-financial support; Taiho: Other: Principal/sub-Investigator of Clinical Trials ; Kyowa: Other: Principal/sub-Investigator of Clinical Trials ; Abbvie: Other: Principal/sub-Investigator of Clinical Trials ; Rohe: Other: Principal/sub-Investigator of Clinical Trials & Non- Financial support; Aduro: Other: Principal/sub-Investigator of Clinical Trials ; Clovis: Other: Principal/sub-Investigator of Clinical Trials ; Takeda: Other: Principal/sub-Investigator of Clinical Trials ; Lysarc: Other: Principal/sub-Investigator of Clinical Trials ; Daiichi Sankyo: Other: Principal/sub-Investigator of Clinical Trials ; Pierre Farbe: Other: Principal/sub-Investigator of Clinical Trials ; Tesaro: Other: Principal/sub-Investigator of Clinical Trials ; Pharmamar: Other: Principal/sub-Investigator of Clinical Trials ; Sanofi: Other: Principal/sub-Investigator of Clinical Trials ; Chugai: Other: Principal/sub-Investigator of Clinical Trials ; Amgen: Other: Principal/sub-Investigator of Clinical Trials ; Oncoethix: Other: Principal/sub-Investigator of Clinical Trials ; Lilly: Other: Principal/sub-Investigator of Clinical Trials ; Celgene: Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; BMS: Honoraria, Other: Principal/sub-Investigator of Clinical Trials & Non-Financial Support; Merus: Other: Principal/sub-Investigator of Clinical Trials ; Gilead: Other: Non-Financial Support; Agios: Other: Principal/sub-Investigator of Clinical Trials ; Sierra Oncology: Other: Principal/sub-Investigator of Clinical Trials ; Xencor: Other: Principal/sub-Investigator of Clinical Trials ; Argen-X: Other: Principal/sub-Investigator of Clinical Trials ; MSD: Other: Principal/sub-Investigator of Clinical Trials ; Loxo: Other: Principal/sub-Investigator of Clinical Trials ; Octimet: Other: Principal/sub-Investigator of Clinical Trials ; Bayer: Other: Principal/sub-Investigator of Clinical Trials ; Medimmune: Other: Principal/sub-Investigator of Clinical Trials ; Lytix Biopharma: Other: Principal/sub-Investigator of Clinical Trials ; Beigene: Other: Principal/sub-Investigator of Clinical Trials ; Blueprint: Other: Principal/sub-Investigator of Clinical Trials ; Aveo Pharmaceuticals: Other: Principal/sub-Investigator of Clinical Trials ; Exelixis: Other: Principal/sub-Investigator of Clinical Trials ; Forma: Other: Principal/sub-Investigator of Clinical Trials ; Gamamabs: Other: Principal/sub-Investigator of Clinical Trials ; Genentech: Other: Principal/sub-Investigator of Clinical Trials ; Gortec: Other: Principal/sub-Investigator of Clinical Trials ; GSK: Other: Principal/sub-Investigator of Clinical Trials ; H3 Biomedecine: Other: Principal/sub-Investigator of Clinical Trials ; Incyte: Other: Principal/sub-Investigator of Clinical Trials ; Innate Pharma: Other: Principal/sub-Investigator of Clinical Trials . Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Maerevoet: abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; roche: Other: travel grant; takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Ribrag: Servier: Consultancy, Honoraria; Amgen: Research Funding; BMS: Consultancy, Honoraria, Other: travel; Incyte Corporation: Consultancy; Infinity: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; MSD: Honoraria; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; argenX: Research Funding; epizyme: Consultancy, Honoraria; pharmamar: Other: travel.

*signifies non-member of ASH