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2818 Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Clinical: Poster II
Hematology Disease Topics & Pathways:
Biological, Lymphoid Leukemias, ALL, Non-Hodgkin Lymphoma, Lymphomas, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Plasma Cell Disorders, B Cell Lymphoma, Clinically Relevant, Diseases, SARS-CoV-2/COVID-19, Real World Evidence, Therapies, Infectious Diseases, Lymphoid Malignancies, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Anne Mea Spanjaart, MD1*, Per Ljungman, MD, PhD2, Rafael De La Camara, MD3, Gloria Tridello4*, Valentín Ortiz-Maldonado, MD, PhD5*, Alvaro Urbano-Ispizua, MD, PhD5, Pere Barba, MD, PhD6*, Mi Kwon, MD, PhD7*, Dolores Caballero, MD8, Pierre Sesques, MD9*, Emmanuel Bachy, MD, PhD10*, Roberta Di Blasi, MD, PhD11*, Catherine Thieblemont, MD, PhD11, Friso Calkoen12*, Pim G.N.J. Mutsaers, MD, PhD13*, Johan A. Maertens, MD, PhD14*, Livia Giannoni, MD15*, Emma Nicholson, MD, PhD16*, Matthew P. Collin, MD, PhD17, Carlos Pinho Vaz, MD18*, Elisabetta Metafuni19*, Joaquín Martínez-López20*, Fiona Dignan, MD, FRCP, FRCPath21*, Josep-Maria Ribera, MD, PhD22, Arnon Nagler, M.D.23, František Folber, MD, PhD24*, Robin Sanderson, PhD25, Adrian Bloor, MD, PhD, FRCP, FRCPath26*, Fabio Ciceri, MD27*, Nina Knelange28*, Francis A. Ayuk, MD29*, Nicolaus Kröger, MD29*, Marie José Kersten, MD, PhD30 and Stephan Mielke, MD31

1Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam and LYMMCARE, Amsterdam, Netherlands
2Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
3Department of Hematology, Hospital Universitario de La Princesa, Madrid, Spain
4Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
5Department of Hematology, Hospital Clinic de Barcelona, Barcelona, Spain
6Department of Hematology, Vall d’Hebron University Hospital, University Hospital Vall d’Hebron, Barcelona, Spain
7Department of Hematology, Hospital General Universitario Gregorio Marañón, Gregorio Marañon Health Research Institute, Madrid, Spain
8Department of Hematology, Hospital Universitario de Salamanca (HUS/IBSAL) and CIBERONC, Salamanca, Spain
9Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Benite, France
10Department of Hematology, Lyon Sud Hospital, Lyon, France
11Department of Hematology, Assistance Publique Hôpitaux de Paris - Hopital Saint-Louis, University of Paris, Paris, France
12Princess Maxima Centre for Pediatric Oncology, Utrecht, Netherlands
13Department of Hematology, Erasmus MC Cancer Center, Rotterdam, Netherlands
14Deptartment of Hematology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
15Ematologia e Centro Trapianti, IRCCS Ospedale Policlinico San Martino, Genova, Italy
16Department of Hematology, The Royal Marsden Hospital, University College London, London, GBR
17Adult HSCT unit, Northern Centre for Bone Marrow Transplantation, Newcastle Upon Tyne, United Kingdom
18BMT Unit, Instituto Português de Oncologia do Porto, Porto, Portugal
19Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione policlinico gemelli IRCSS, Rome, Italy
20Department of Hematology, Hospital Univ. 12 de Octubre, Complutense University, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
21Clinical Haematology Department, Manchester Royal Infirmary, Manchester, GBR
22Clinical Hematology Department, Ico-Hospital Universitari Germans Trias Y Pujol, Badalona, Barcelona, Spain
23Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
24Department of Internal Medicine - Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
25Department of Haematological Medicine, Barts Cancer Institute, London, Eng, United Kingdom
26Adult Leukaemia and Bone Marrow Transplant Unit, The Christie Hospital NHS Foundation Trust, University of Manchester, Manchester, United Kingdom
27Haematology and BMT, Ospedale San Raffaele s.r.l., Milano, Italy
28EBMT Data Office, Leiden, Netherlands
29Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany
30Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands and LYMMCARE, Amsterdam, Netherlands
31Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Dept. of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

Background

The ongoing Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is having an enormous impact on society worldwide and is especially posing a threat to health in vulnerable patients, such as patients with immune deficiencies. It is expected that patients who received Chimeric Antigen Receptor T-cell (CAR T-cell) therapy for hematologic malignancies are at risk for poor outcomes after COVID-19 due to their severely immunocompromised state caused by prior cumulative immunochemotherapy, on-target/off-tumor B-cell depletion, hypogammaglobulinemia and ongoing cytopenias. Current data are limited to small case series and case reports. This study describes the clinical characteristics and outcomes of CAR T-cell therapy recipients after developing COVID-19 in the largest cohort to date.

Methods

In response to the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation (EBMT) developed a special COVID-19 report form to capture data from all patients with COVID-19 after treatment with CAR T-cell therapy for hematologic malignancies. Only PCR positive SARS-CoV-2 diagnosed patients before June 1st, 2021 were included. The aim of this study was to describe the clinical course after COVID-19 diagnosis and evaluate overall survival. Overall survival probabilities were calculated using the Kaplan Meier method. Factors associated with mortality after COVID-19 diagnosis were examined using a Cox proportional hazard model.

Results

A total of 57 patients from 11 countries were reported to the EBMT. One patient with incomplete data at diagnosis and without any follow up information had to be excluded from the analysis. The median age of these 56 patients was 57.7 years (min-max 5.2 - 72.8) including 55 adults and one child. Of these patients, 32 were male. CAR T-cell therapy was given to 46 patients with B-cell-non-Hodgkin lymphoma, 7 patients with B-cell acute lymphoblastic leukemia, and 3 patients with multiple myeloma. The median time from CAR T-cell infusion to COVID-19 diagnosis was 7.4 months (min-max 0.03 - 25.3). At the time of COVID-19 diagnosis, 62.5% of patients were in complete remission, 12.5% of patients had a partial response and 25% of patients had relapsed/refractory disease. Forty-five patients (80%) were admitted to hospital (median 26,5 days, min-max 3-171) due to COVID-19. Of the admitted patients, 24 (53%) needed oxygen support. Twenty-two (49%) patients were admitted to the intensive care unit (median 14 days, min - max 2-65) and 16 (73%) of these patients received invasive ventilation. At the time of analysis, 25 of the 56 patients had died (44.6%), most (23/25) due to COVID-19, resulting in a COVID-19 attributable mortality rate of 41%. The Kaplan-Meier estimate of overall survival is shown in Figure 1. The median follow-up from COVID-19 diagnosis was 20.9 weeks. In 1 of the 32 alive patients there was no resolution of COVID-19 at the time of analysis. In multivariate analysis, older age (hazard ratio (HR) 1.50, 95% CI 1.11-2.03, p=0.009) and comorbidities (HR 2.56, 95% CI 1.05-6.23, p=0.001) had a negative impact on overall survival. Better performance status at time of admission (HR 0.72, 95% CI 0.59-0.88, p=0.038) had a positive impact on overall survival. Sex, time from CAR T-cell therapy to COVID-19 diagnosis, disease remission status and the occurrence of neurotoxicity or cytokine release syndrome after CAR T-cell infusion did not have a significant effect on overall survival in the multivariate analysis.

Conclusion

Patients with COVID-19 after B-cell-targeted CAR T-cell therapy have a very poor outcome. As it remains uncertain whether currently applied vaccination strategies against SARS-CoV-2 are effective after CAR T-cell therapy, vaccination of health-care personnel and family members in combination with protective measures against viral exposure are likely to play the most important role in protecting this vulnerable group of patients. Better treatment strategies are urgently needed.

Disclosures: Ljungman: Enanta: Other: DSMB; Janssen: Other: Investigator; Blueprint Medicines: Other: DSMB; OctaPharma: Other: DSMB; Merck: Other: Investigator, speaker; Takeda: Consultancy, Other: Endpoint committee, speaker; AiCuris: Consultancy; Pfizer: Other: Speaker. De La Camara: IQONE: Consultancy; Roche: Consultancy. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Barba: Novartis: Honoraria; Gilead: Honoraria; BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Sesques: Novartis: Honoraria; Chugai: Honoraria; Kite, a Gilead Company: Honoraria. Bachy: Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Honoraria. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Thieblemont: Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Nicholson: Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees; BMS/Celgene: Consultancy; Pfizer: Consultancy. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Ribera: NOVARTIS: Consultancy, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; ARIAD: Consultancy, Research Funding, Speakers Bureau; SHIRE: Consultancy, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Sanderson: Kite, a Gilead Company: Honoraria; Novartis: Honoraria. Bloor: Kite, a Gilead Company: Honoraria; Novartis: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Ayuk: Novartis: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Gilead: Honoraria; Miltenyi Biomedicine: Honoraria; Celgene/BMS: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Kersten: Celgene: Research Funding; Novartis: Consultancy, Honoraria, Other: Travel support; Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Mielke: Novartis: Speakers Bureau; Immunicum: Other: Data safety monitoring board; DNA Prime SA: Speakers Bureau; Gilead/KITE: Other: Travel support, Expert panel ; Miltenyi: Other: Data safety monitoring board; Celgene/BMS: Speakers Bureau.

*signifies non-member of ASH