Outcomes of Breakthrough COVID-19 Infections in Patients with Hematologic Malignancies

Background: Cancer patients (pts), especially those with hematologic malignancies, have not only an increased risk for SARS-CoV2 infections, but also a higher risk of morbidity and mortality. Pts with hematologic malignancies have lower seroconversion rates post-vaccination, leading to concern for poor clinical outcomes despite vaccination. Here, we evaluated clinical outcomes of COVID-19 infections in both vaccinated and unvaccinated pts with hematologic malignancies.

Methods: We retrospectively analyzed pts with hematologic malignancies at a The University of Texas MD Anderson Cancer Center who contracted COVID-19 between December 2020 (after the availability of vaccinations) and October 2021 (prior to the emergence of the Omicron variant). Patient demographics/clinical data, COVID-19 vaccination and infection dates, and outcomes were collected using an institutional database with Syntropy and the Foundry platform and confirmed by manual review of patient records by the first and last authors. Statistical analyses were performed using R version 4.1.3.

Results: A total of 418 pts with hematologic malignancies contracted SARS-CoV2: 243 vaccinated pts and 175 unvaccinated pts. In the vaccinated group, 76 pts (31.3%) were hospitalized for COVID-19 infections, while 92 unvaccinated pts (52.6%) were hospitalized (p≤0.001). Regarding mechanical ventilation, 12 vaccinated (4.9%) and 15 unvaccinated (8.6%) pts were intubated during their COVID-19-associated hospitalizations (p=0.20). There were 47 deaths due to any cause, with 24 deaths among vaccinated pts and 23 among unvaccinated pts. Among these, 32 deaths were due to COVID-19, with 17 in the vaccinated cohort (rate of death 7.0%, 95% confidence interval (CI): 4.3-11.1) and 15 in the unvaccinated group (rate of death 8.6%, 95% CI: 5.0-14.0). There were no significant differences in COVID-19-associated deaths between the 2 cohorts (p=0.61).

The association of vaccination status, age, gender, modified Charlson Comorbity Index (CCI), and disease group (B-cell lymphoma, plasma cell dyscrasia, other hematologic malignancy) with the risk of death from COVID-19 infections was explored by univariate logistic regression. Females (odds ratio (OR) 2.77, p=0.01), older pts (OR 1.03, p=0.02), and individuals with more comorbidities according to the modified CCI (OR 1.32, p=0.003) were at a higher risk of death from COVID-19 infections. There was no statistically significant association between vaccination status or disease type and the risk of death from COVID-19. To account for the non-randomized nature of COVID-19 vaccination status, a propensity score weighting approach was utilized. In the final propensity weighted model, vaccination status was not significantly associated with risk of death from COVID-19 infections (OR 0.70, 95% CI: 0.33-1.50, p=0.36). The predicted benefit of vaccination was a decrease in the probability of death from COVID-19 infections by 2.3%.

Conclusion: COVID-19 vaccination status in pts with hematologic malignancies was associated with a decreased risk for hospitalization but not associated with a decreased the risk of death from COVID-19 infections. Though rates of death are lower than previously reported, mortality remained high for pts with hematologic malignancies who contracted COVID-19 in the pre-Omicron era. Protective strategies, in addition to immunization, are warranted in this vulnerable patient population, including pre-exposure prophylaxis with tixagevimab-cilgavimab and early utilization of protease inhibitors in those who test positive for COVID-19.

Chihara:Eisai: Honoraria; AstraZeneca: Honoraria. Thompson:AbbVie, Pharmacyclics, Adaptive Biotechnologies, Genentech: Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; AbbVie, Gilead, Janssen, Pharmacyclics, Adaptive Biotechnologies, Genentech: Consultancy; AbbVie, Gilead, Janssen, Pharmacyclics, Adaptive Biotechnologies, Genentech, Amgen: Honoraria.