SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report
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 ra...
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BMJ Publishing Group
2023-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/1/e005957.full |
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| author | Hongyan Liu Colleen Callahan Shannon L Maude Kevin Owen McNerney Rebecca M Richards Paibel Aguayo-Hiraldo Friso G Calkoen Julie-An Talano Amy Moskop Adriana Balduzzi Jennifer Krajewski Hema Dave Anant Vatsayan Yimei Li Kara Lynn Davis |
| author_facet | Hongyan Liu Colleen Callahan Shannon L Maude Kevin Owen McNerney Rebecca M Richards Paibel Aguayo-Hiraldo Friso G Calkoen Julie-An Talano Amy Moskop Adriana Balduzzi Jennifer Krajewski Hema Dave Anant Vatsayan Yimei Li Kara Lynn Davis |
| author_sort | Hongyan Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6172d8b90c9540918dcb40c5c533faf9 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-6172d8b90c9540918dcb40c5c533faf92025-01-29T10:45:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-005957SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry reportHongyan Liu0Colleen Callahan1Shannon L Maude2Kevin Owen McNerney3Rebecca M Richards4Paibel Aguayo-Hiraldo5Friso G Calkoen6Julie-An Talano7Amy Moskop8Adriana Balduzzi9Jennifer Krajewski10Hema Dave11Anant Vatsayan12Yimei Li13Kara Lynn Davis14College of Public Health, Chongqing Medical University, Chongqing, ChinaDivision of Oncology and Cancer Immunotherapy Program, The Children`s Hospital of Philadelphia, Philadelphia, Pennsylvania, USADepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAOncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAHematology, Oncology, and Bone Marrow Transplant, University of Wisconsin-Madison, Madison, Wisconsin, USACancer and Blood Disease Institute, Keck School of Medicine of USC, Los Angeles, California, USADivision of Pediatric Oncology, Princess Maxima Center, Utrecht, The NetherlandsDivision of Hematology/Oncology/Blood and Marrow TransplantationDepartment of Pediatrics, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, Wisconsin, USADivision of Hematology/Oncology/Blood and Marrow TransplantationDepartment of Pediatrics, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, Wisconsin, USAClinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione IRCCS San Gerardo dai Tintori, Milan, ItalyPediatric Blood and Marrow Transplantation, Hackensack Meridian School of Medicine, Hackensack, New Jersey, USACancer Immunology and Microbial Oncology Research Program, Children`s National Hospital, Washington, District of Columbia, USACenter for Cancer and Blood Disorders, Children`s National Hospital, Washington, District of Columbia, USADepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USAPediatrics, Stanford University School of Medicine, Stanford, California, USABackground 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.https://jitc.bmj.com/content/11/1/e005957.full |
| spellingShingle | Hongyan Liu Colleen Callahan Shannon L Maude Kevin Owen McNerney Rebecca M Richards Paibel Aguayo-Hiraldo Friso G Calkoen Julie-An Talano Amy Moskop Adriana Balduzzi Jennifer Krajewski Hema Dave Anant Vatsayan Yimei Li Kara Lynn Davis SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report Journal for ImmunoTherapy of Cancer |
| title | SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report |
| title_full | SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report |
| title_fullStr | SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report |
| title_full_unstemmed | SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report |
| title_short | SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report |
| title_sort | sars cov 2 infections in pediatric and young adult recipients of chimeric antigen receptor t cell therapy an international registry report |
| url | https://jitc.bmj.com/content/11/1/e005957.full |
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