Outcomes and management of the SARS-CoV2 omicron variant in recipients of hematopoietic cell transplantation and chimeric antigen receptor T cell therapy Journal Article
| Authors: | Infante, M. S.; Nemirovsky, D.; Devlin, S.; DeWolf, S.; Tamari, R.; Dahi, P. B.; Lee, Y. J.; Chung, D. J.; Politikos, I.; Barker, J.; Giralt, S. A.; Babady, N. E.; Ramanathan, L.; Papanicolaou, G. A.; Seo, S.; Kamboj, M.; Perales, M. A.; Shah, G. L. |
| Article Title: | Outcomes and management of the SARS-CoV2 omicron variant in recipients of hematopoietic cell transplantation and chimeric antigen receptor T cell therapy |
| Abstract: | Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell therapy (CAR-T) recipients who develop Coronavirus disease 2019 (COVID-19) can have decreased overall survival (OS), likely due to disease-inherent and therapy-related immunodeficiency. The availability of COVID-19-directed therapies and vaccines have improved COVID-19-related outcomes, but immunocompromised individuals remain vulnerable. Specifically, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections, including Omicron and its sublineages, particularly in HCT recipients, remain to be defined. The aim of this study was to compare the impact of SARS-CoV-2 Omicron infections in HCT/CAR-T recipients with outcomes previously reported for ancestral SARS-CoV-2 infections early in the pandemic (March to June 2020). This was a retrospective analysis of adult HCT/CAR-T recipients diagnosed with COVID-19 at Memorial Sloan Kettering Cancer Center between July 2021 and July 2022. We identified 353 patients (172 autologous HCT recipients [49%], 152 allogeneic HCT recipients [43%], and 29 CAR-T recipients [8%]), with a median time from HCT/CAR-T to SARS-CoV-2 infection of 1010 days (interquartile range, 300 to 2046 days). Forty-one patients (12%) were diagnosed with COVID-19 during the delta wave, and 312 patients (88%) were diagnosed during the Omicron wave. Risk factors associated with increased odds of COVID-19-related hospitalization were the presence of 2 or more comorbidities (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.4 to 10.7; P <.001), CAR-T therapy compared to allogeneic HCT (OR, 7.7; 95% CI, 3.0 to 20.0; P <.001), hypogammaglobulinemia (OR, 2.71; 95% CI, 1.06 to 6.40; P =.027), and age at COVID-19 diagnosis (OR, 1.03; 95% CI, 1.0 to 1.05; P =.04). In contrast, infection during the Omicron variant BA5/BA4-dominant period compared to variant BA1 (OR,.21; 95% CI,.03 to.73; P =.037) and more than 3 years from HCT/CAR-T therapy to COVID-19 diagnosis compared to early infection at <100 days (OR,.31; 95% CI,.12 to.79; P =.011) were associated with a decreased odds for hospitalization. The OS at 12 months from COVID-19 diagnosis was 89% (95% CI, 84% to 94%), with 6 of 26 deaths attributable to COVID-19. Patients with the ancestral strain of SAR-CoV-2 had a lower OS at 12 months, with 73% (95% CI, 62% to 84%) versus 89% (95% CI, 84% to 94%; P <.001) in the Omicron cohort. Specific COVID-19 treatment was administered in 62% of patients, and 84% were vaccinated with mRNA COVID-19 vaccines. Vaccinated patients had significantly better OS than unvaccinated patients (90% [95% CI, 86% to 95%] versus 82% [95% CI, 72% to 94%] at 12 months; P =.003). No significant difference in OS was observed in patients infected with the Omicron and those infected with the Delta variant (P =.4) or treated with specific COVID-19 treatments compared with those not treated (P =.2). We observed higher OS in HCT and CAR-T recipients infected with the Omicron variants compared to those infected with the ancestral strain of SARS-CoV2. The use of COVID-19 antivirals, mAbs, and vaccines might have contributed to the improved outcomes. © 2023 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; controlled study; aged; retrospective studies; major clinical study; overall survival; genetics; prednisone; disease course; hypertension; outcome assessment; cohort analysis; plasmacytoma; hematopoietic stem cell transplantation; retrospective study; risk factor; hodgkin disease; hospitalization; disease severity; myeloablative conditioning; myelodysplastic syndrome; immune response; virus rna; vaccination; comorbidity; chimeric antigen receptor; allogeneic hematopoietic stem cell transplantation; hydroxychloroquine; methylprednisolone; azithromycin; immunoglobulin deficiency; hyperlipidemia; graft recipient; autologous hematopoietic stem cell transplantation; myeloproliferative neoplasm; rna, viral; non-hodgkin lymphoma; genotyping; plasma cell dyscrasia; pandemic; acetylcysteine; tocilizumab; humans; human; male; female; article; siltuximab; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; serologic response; axicabtagene ciloleucel; lisocabtagene maraleucel; anakinra; severe acute respiratory syndrome coronavirus 2; coronavirus disease 2019; covid-19; sars-cov-2; receptors, chimeric antigen; convalescent plasma; remdesivir; covid-19 testing; nasopharyngeal swab; brexucabtagene autoleucel; covid-19 vaccines; sars-cov-2 vaccine; cilgavimab plus tixagevimab; sotrovimab; sars-cov-2 omicron; sars-cov-2 delta; vaccinee; idecabtagene vicleucel; molnupiravir; nirmatrelvir plus ritonavir; bebtelovimab; covid-19 infection; covid-19 therapy; hct and car-t patients; covid-19 drug treatment; sars-cov-2 variants; bamlanivimab; bamlanivimab plus etesevimab; casirivimab plus imdevimab; covid-19 pharmacotherapy |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 30 |
| Issue: | 1 |
| ISSN: | 2666-6367 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-01-01 |
| Start Page: | 116.e1 |
| End Page: | 116.e12 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2023.09.027 |
| PUBMED: | 37806446 |
| PROVIDER: | scopus |
| PMCID: | PMC11220618 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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