Outcomes and Management of SARS-CoV2 Omicron Variant in Recipients of Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T cell (CART) therapy.

BACKGROUND: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell therapy (CART) recipients who develop COVID-19 can have decreased overall survival, 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 SARS-CoV-2 variant infections, including Omicron and its sublineages, particularly in transplant recipients, are yet to be defined. The aim of this study was to compare the impact of SARS-CoV-2 Omicron infections in HCT/CART recipients with outcomes previously reported for ancestral SARS-CoV-2 infections early in the pandemic (March-June 2020).

STUDY DESIGN: Retrospective analysis adult HCT/CART recipients diagnosed with COVID-19 at Memorial Sloan Kettering Cancer Center (MSKCC), New York, between July 2021 and July 2022.

RESULTS: We identified 353 patients (172 auto, 49%; 152 allo, 43%; 29 CART, 8%) with a median time from HCT/CART to SARS-CoV-2 infection of 1010 days (IQR, 300 to 2046). Forty-one (12%) patients were diagnosed with COVID-19 during the delta wave and 312 (88%) patients during the Omicron wave. Risk factors associated with increased odds of COVID-19 related hospitalization were the presence of 2 or more comorbidities (OR, 4.9; 95% CI 2.4-10.7, p< 0.001), CART therapy compared to allogeneic HCT (OR 7.7; 95% CI 3.0-20.0, p<0.001), hypogammaglobulinemia (OR 2.71; 95% CI 1.06-6.40, p=0.027), and age at COVID-19 diagnosis (OR 1.03; 95% CI 1.0-1.05, p= 0.04). In contrast, infection during Omicron variant BA5/BA4 dominant period compared to variant BA1 (OR 0.21; 95% CI 0.03-0.73, p =0.037), and more than 3 years from HCT/CART therapy to COVID-19 diagnosis, compared to early infection < 100 days (OR 0.31; 95% CI 0.12-0.79, p=0.011) were associated with a decreased odds for hospitalization. The overall survival (OS) at 12 months from COVID-19 diagnosis was 89% (95% CI: 84-94%), with 6/26 deaths attributable to COVID-19. Patients with the ancestral strain of SAR-CoV-2 had a lower overall survival at 12 months, with 73% (95% CI: 62-84%) vs 89% (95% CI: 84-94%), (p<0.001) 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, being 90% (95% CI: 86-95%) vs 82% (95% CI: 72-94%) at 12 months, respectively (p=0.003). No significant difference in OS was observed in patients infected with the Omicron vs with Delta variant (p=0.4) or treated with specific COVID-19 treatments vs those not treated (p=0.2).

CONCLUSIONS: We observed higher overall survival in HCT and CART recipients infected with the Omicron variants compared to the ancestral strain of SARS-CoV2. Use of COVID-19 antivirals, monoclonal antibodies, and vaccines may have contributed to improved outcomes.