Breakthrough COVID-19 in vaccinated patients with haematologic malignancies

January 2023 Covid-19 Jolien Blokken

Results from the EPICOVIDEHA registry demonstrate that the mortality rate in patients with haematologic malignancies with breakthrough COVID-19 is around 9%, which is significantly lower than that in the pre-vaccination era. Furthermore, patients who received monoclonal antibodies, alone or combined with antivirals, showed a better clinical outcome.

In April 2020, the European Hematology Association’s Specialized Working Group, Infections in Hematology, opened the EPICOVIDEHA (Epidemiology of COVID-19 Infection in Patients with Hematological Malignancies: European Hematology Association) registry to collect data on all adult patients with haematologic malignancies (HM) who developed COVID-19. Based on the data available in this registry, researchers now analysed the epidemiology and outcome of breakthrough COVID-19 in a large cohort of patients with HMs and evaluated anti-SARS-CoV-2 treatment received by these patients.

Adult patients with HM, at least one dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analysed. A total of 1,548 cases were included, mainly lymphoid malignancies (1,181 cases, 76%). COVID-19 was mild, severe, or critical in 39%, 32.9%, and 9.8% of cases, respectively. Researchers found a significantly lower rate of severe or critical cases compared with what was reported in the pre-vaccination era (pre-vaccination 63.8% vs. post-vaccination 42.7%; p< 0.001). Viral genomes were studied in 753 cases (48.6%), with the different Omicron variant the most frequently detected viral strain (68.7%). Most patients received 2 or 3 anti-SARS-CoV-2 vaccine doses (91%), mostly with mRNA-based technology (89%) and only a few patients (8.6%) received a vector-based vaccine and a minority of them an inactivated vaccine. Overall, 58.5% of patients received a specific treatment for COVID-19, whereas 41.5% were not treated or received symptomatic therapies. Overall day-30 mortality was 9.2%, which is significantly lower than that reported in the pre-vaccine era (pre-vaccine 31.2% vs. post-vaccine 9.2%; p< 0.001). There was no significant difference in terms of 30-day mortality rate among the different HM (p= 0.693), in contrast to that observed in the pre-vaccination era in which there was a higher number of fatalities in patients with AML/myelodysplastic syndrome.

In the univariable analysis, older age (p< 0.001), active HM (p< 0.001), and severe and critical COVID-19 (p= 0.007 and p< 0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p< 0.001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (p< 0.001) or combined with antivirals (p= 0.009), was protective.


Results from the EPICOVIDEHA registry show that vaccination and novel COVID-19 treatments have brought significant improvements in terms of mortality in patients with HM. To further improve the prognosis of these patients, the role of additional booster vaccine doses and the role of prophylactic monoclonal antibodies in patients with an ineffective response to vaccination should be investigated.


Pagano L, et al. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey. Blood. 2022;140(26):2773-87.