COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2-78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020-2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.

Adult HSCT unit Northern Centre for Bone Marrow Transplantation Newcastle Tyne UK

Adult Leukaemia and Bone Marrow Transplant Unit Christie NHS Foundation Trust Hospital University of Manchester Manchester UK

Blood and Bone Marrow Transplantation Department University Hospital of Cardiff Cardiff UK

Cell Therapy and Transfusion Medicine Unit Azienda Ospedaliero Universitaria Careggi Firenze Italy

Cellular Therapy and immunobiology working party of EBMT

Celular Therapy Department Instituto Portugués de Oncologia do Porto Francisco Gentil E P E Porto Portugal

Chaim Sheba Medical Center Tel Aviv University Tel Hashomer Israel

Clinical Hematology Department Catalan Institute of Oncology Hospital Germans Trias i Pujol Josep Carreras Research Institute Barcelona Spain

Department for Children and Adolescents Division for Stem Cell Transplantation and Immunology University Hospital Frankfurt Goethe University Frankfurt Germany

Department of Cellular Therapy and Allogeneic Stem Cell Transplantation Department of Laboratory Medicine Karolinska Institutet and University Hospital Karolinska Comprehensive Cancer Center Karolinska ATMP Center Stockholm Sweden

Department of Cellular Therapy and Allogeneic Stem Cell Transplantation Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center Stockholm Sweden

Department of Clinical Haematology Manchester Royal Infirmary Manchester University NHS Foundation Trust Manchester UK

Department of Haematology The Royal Marsden Hospital London United Kingdom

Department of Haematology University College London Hospital London UK

Department of Haematology University Hospitals Bristol and Weston NHSFT Bristol UK

Department of Hematology Amsterdam UMC location University of Amsterdam Cancer Center Amsterdam and LYMMCARE Amsterdam The Netherlands

Department of Hematology and Cellular Therapy IRCCS Ospedale Policlinico San Martino Genova Italy

Department of Hematology Assistance Publique Hôpitaux de Paris Hopital Saint Louis Paris France

Department of Hematology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Hematology Department of Internal Medicine Division of Hematology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht Netherlands

Department of Hematology Erasmus MC Cancer Center Rotterdam the Netherlands

Department of Hematology Hospices Civils de Lyon Lyon Sud Hospital Pierre Bénite France

Department of Hematology Hospital Clínic Barcelona Spain

Department of Hematology Hospital G Universitario Gregorio Marañon Institute of Health Research Gregorio Marañon Madrid Spain

Department of Hematology Hospital Univ 12 de Octubre Complutense University CNIO Madrid Spain

Department of Hematology Hospital Universitario de La Princesa Madrid Spain

Department of Hematology Hospital Universitario de Salamanca and IBSAL Salamanca Spain

Department of Hematology Leiden University Medical Center Leiden Netherlands

Department of Hematology Oncology Stem Cell Transplantation Faculty of Medicine and Medical Center University of Freiburg Freiburg im Breisgau Germany

Department of Hematology University Medical Center Groningen University of Groningen Groningen Netherlands

Department of Hematology University Medical Center Utrecht Utrecht Netherlands

Department of Hematology Vall d'Hebron University Hospital Barcelona Spain

Department of internal Medicine Hematology and Oncology Masaryk University Hospital Brno Brno Czech Republic

Department of Stem cell Transplantation University Hospital Eppendorf Hamburg Germany

Deptartment of Hematology University Hospital Gasthuisberg Leuven Belgium

Dipartimento di Diagnostica per Immagini Radioterapia Oncologica e Ematologia Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

European Society for Blood and Marrow Transplantation Data Office Department of Medical Statistics and Bioinformatics Leiden Netherlands

European Society for Blood and Marrow Transplantation Data Office Leiden Netherlands

Hematology and BMT Unit IRCCS San Raffaele Scientific Institute Milan Italy

King's College Hospital NHS Foundation Trust Department of Haematological Medicine Denmark Hill London UK

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

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