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
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus
Citation Impact
MSK Authors
  1. Ngolela Esther Babady
    145 Babady
  2. Susan Seo
    108 Seo
  3. Yeon Joo Lee
    45 Lee
  4. Sergio Andres Giralt
    953 Giralt
  5. Mini Kamboj
    137 Kamboj
  6. Miguel-Angel Perales
    802 Perales
  7. Juliet N Barker
    332 Barker
  8. David Chung
    192 Chung
  9. Sean McCarthy Devlin
    547 Devlin
  10. Parastoo Bahrami Dahi
    247 Dahi
  11. Roni Tamari
    193 Tamari
  12. Gunjan Lalitchandra Shah
    317 Shah
  13. Susan E Dewolf
    22 Dewolf