COVID-19 breakthrough infections, hospitalizations and mortality in fully vaccinated patients with hematologic malignancies: A clarion call for maintaining mitigation and ramping-up research.

There has been limited data presented to characterize and quantify breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with hematologic malignancies (HM). We performed a retrospective cohort study of patient electronic health records of 514,413 fully vaccinated patients from 63 healthcare organizations in the US, including 5956 with HM and 508,457 without malignancies during the period from December 2020 to October 2021. The breakthrough SARS-CoV-2 infections in patients with HM steadily increased and reached 67.7 cases per 1000 persons in October 2021. The cumulative risk of breakthrough infections during the period in patients with HM was 13.4%, ranging from 11.0% for acute lymphocytic leukemia to 17.2% and 17.4% for multiple myeloma and chronic myeloid leukemia respectively, all higher than the risk of 4.5% in patients without malignancies (p < 0.001). No significant racial disparities in breakthrough infections were observed. The overall hospitalization risk was 37.8% for patients with HM who had breakthrough infections, significantly higher than 2.2% for those who had no breakthrough infections (hazard ratio or HR: 34.49, 95% CI: 25.93-45.87). The overall mortality risk was 5.7% for patients with HM who had breakthrough infections, significantly higher than the 0.8% for those who had no breakthrough infections (HR: 10.25, 95% CI: 5.94-17.69). In summary, this study shows that among the fully vaccinated population, patients with HM had significantly higher risk for breakthrough infections compared to patients without cancer and that breakthrough infections in patients with HM were associated with significant clinical outcomes including hospitalizations and mortality.