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Patients with hematologic malignancies who had breakthrough COVID-19 infections still had high risk for severe or critical disease, according to a registry-based study.

Out of 113 reported cases of SARS-CoV-2 infection post-vaccination in people with blood cancers, 79 (60.4%) experienced severe or critical disease, with 75 requiring hospitalization, reported Livio Pagano, MD, of the Università Cattolica del Sacro Cuore in Rome, and colleagues.

Among the hospitalized patients, 16 were admitted into an ICU and 10 of those required mechanical ventilation. At 30-day follow-up after COVID-19 diagnosis, 14 patients had died (12.3% of the infected patients), with all but one death determined to be caused by COVID-19, they stated in a letter in .

Pagano's group used data from the registry, which tracks patients with blood cancers who contract COVID-19. They cautioned that this preliminary study was limited by the low numbers of reported cases. But it is the first to report on the incidence and nature of post-vaccination COVID-19 cases in patients with hematologic malignancies, they pointed out.

"Importantly, the overall mortality observed in our patients, although lower than in the pre-vaccination period, remained high," they wrote. "This percentage, on one hand, remains quite worrying for hematologists, but on the other hand should be interpreted as a significant achievement following the spread of vaccination programs around the world."

But the fact remains that the proportion of patients in this study who landed in the hospital, and were admitted to an ICU, was quite high, noted Samir Parekh, MBBS, of the Icahn School of Medicine at Mount Sinai in New York City.

He told 麻豆传媒 that he and his colleagues will recommend passive monoclonal antibody treatment for patients with breakthrough infections, as that treatment has "has been successful in preventing worsening outcomes."

"I wonder if the individuals [in this study] had access to those," added Parekh, who was not involved in the study.

While Pagano and colleagues did not specifically address passive monoclonal antibody treatment, they noted that "the low serologic response rate to anti-SARS-CoV-2 vaccines in patients with [hematologic malignancies] may translate to higher rates of infections. This has previously been described following monoclonal antibody treatment," citing studies from the , , and .

In Early November, the CDC updated its for COVID-19 vaccine use, including new guidance for people who receive passive antibody products.

The European Hematology Association-Infectious Diseases Working Party (EHA-IDWP) opened the EPICOVIDEHA registry in April 2020, with participating institutions reporting 3,801 valid cases of COVID-19, with a mortality rate of 31%.

Starting Jan. 1, 2021, Pagano and colleagues retrospectively collected registry data on fully or partially vaccinated adult patients who contracted COVID-19 infections. The cases of breakthrough COVID-19 cases were recorded as of August 2021, and were reported by about one-quarter of the registry's participating institutions. The majority of patients in the current study were male (61.1%) and over age 50 (85.8%).

The authors found that post-vaccine IgG levels against SARS-CoV-2 spike protein were analyzed in 40 (35.4%) of the 113 infected patients, with only 13 achieving an antibody response, and the remainder considered non-responders.

More than 80% of these patients had underlying lymphoproliferative malignancies, such as chronic lymphoid leukemia, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, Hodgkin's lymphoma, and multiple myeloma.

"Unfortunately, people with lymphomas are more likely to have suppressed immune systems and to develop infections, and it is no different for COVID-19," Pagano said in a statement. "In future studies we will look at the efficacy of additional vaccine doses to understand if they can reduce infection in our patients, especially those with lymphoproliferative disorders."

The authors reported that 68.1% of the patients received active treatment for underlying hematological malignancies at the time of or within the prior 3 months of vaccination. The majority received either BioNTech/Pfizer (69.9%) or Moderna (17.7%) mRNA vaccines, while 12.4% received a vector-based vaccine (AstraZeneca Oxford) or an inactivated vaccine (Sinovac CoronaVac). Also, 87 patients were considered fully vaccinated while 26 got one shot. The median time from the last dose of vaccine and COVID-19 diagnosis was 64 days.

Pagano's group found no statistical difference in terms of mortality between partially or fully vaccinated patients (15.4% vs 11.5%), or between those who achieved a serological response and non-responders (13.3% vs 15.6%). On multivariable analysis, the only factor independently related to the risk of death among the patients was age.

Parekh, who led a study that found multiple myeloma patients were unable to mount a sufficient antibody response, and/or T-cell responses, after COVID-19 vaccination, said the European findings confirmed his group's data that "hematological malignancy patients remain at higher risk for COVID-related morbidity and mortality after two-dose vaccination."

He highlighted that, in the current study, serological testing was done in a subset of patients, and two-thirds did not mount any antibodies, which could "explain why they [patients with hematologic malignancies] are vulnerable and need to have boosters and, if possible, passive antibodies like the ones we have in the U.S." The CDC recommends for people who are moderately to severely immunocompromised.

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