SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report.

Autor:	McNerney KO; Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA kmcnern1@jhmi.edu.; Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Richards RM; Hematology, Oncology, and Bone Marrow Transplant, University of Wisconsin-Madison, Madison, Wisconsin, USA., Aguayo-Hiraldo P; Cancer and Blood Disease Institute, Keck School of Medicine of USC, Los Angeles, California, USA., Calkoen FG; Division of Pediatric Oncology, Princess Maxima Center, Utrecht, The Netherlands., Talano JA; Division of Hematology/Oncology/Blood and Marrow TransplantationDepartment of Pediatrics, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA., Moskop A; Division of Hematology/Oncology/Blood and Marrow TransplantationDepartment of Pediatrics, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA., Balduzzi A; Clinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione IRCCS San Gerardo dai Tintori, Milan, Italy., Krajewski J; Pediatric Blood and Marrow Transplantation, Hackensack Meridian School of Medicine, Hackensack, New Jersey, USA., Dave H; Cancer Immunology and Microbial Oncology Research Program, Children's National Hospital, Washington, District of Columbia, USA., Vatsayan A; Center for Cancer and Blood Disorders, Children's National Hospital, Washington, District of Columbia, USA., Callahan C; Division of Oncology and Cancer Immunotherapy Program, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Liu H; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Li Y; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Davis KL; Pediatrics, Stanford University School of Medicine, Stanford, California, USA.; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, California, USA., Maude SL; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Jan; Vol. 11 (1).
DOI:	10.1136/jitc-2022-005957
Abstrakt:	Background: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited. Methods: We created an international retrospective registry of CAR T recipients aged 0-30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed. Results: Nine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15-30 days. Conclusions: In a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease. Competing Interests: Competing interests: AB: Novartis, Amgen and Medac, speaker’s bureau; Medac, Neovii and Novartis meeting support. SLM: Novartis, advisory boards, study steering committees, clinical trial support; Wugen: advisory board. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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