Patients with a hematologic malignancy, as well as those with benign hematologic conditions, are often immunocompromised, explains Mette D. Hazenberg, MD, PhD.

“This can be related to the condition,” Dr. Hazenberg says. “For example, untreated chronic lymphocytic leukemia
and multiple myeloma are characterized by immune dysfunction that renders patients susceptible to opportunistic infections. However, it often can be related to the treatment these patients are receiving. Many immunotherapies and chemotherapies render patients immunocompromised since they lead to lymphocyte depletion or dysfunction or long lasting neutropenia.”

During the COVID-19 pandemic, it was suspected that patients with a hematologic condition were at increased risk for severe COVID-19 and COVID-19-related death, she continues, which was later confirmed by population-based studies.

“There was a great need to protect these patients, particularly through vaccination,” Dr. Hazenberg says. “At the same time, it was unclear if patients would be able to build up sufficient protection through vaccination since they are immunocompromised. There is not much data on the effect of vaccination as it pertains to the most immunocompromised patients. Therefore, there was a great need to investigate the immunogenicity of COVID-19 vaccinations in patients with hematologic malignancies.”

Do Not Delay Vaccination Due to Expected Lower Immunogenicity

For a study published in JAMA Oncology, Dr. Hazenberg and colleagues investigated whether a third mRNA-1273 vaccination is linked with increased neutralization of antibody concentrations in patients with hematologic cancers who are immunocompromised compared with levels obtained in healthy controls after the standard two dose mRNA vaccination schedule. They conducted a cohort study at four university hospitals and included 584 patients with hematologic cancers, plus 44 randomly selected age-matched controls without malignant or immunodeficient comorbidities (Figure).

A key finding from this investigation, according to the study team, is that it is critical to not postpone vaccination because of anticipated lower immunogenicity. “Antibody concentrations obtained from our patients after the standard two-dose vaccination were lower than in the healthy population, but nevertheless, much higher than expected,” Dr. Hazenberg notes. “In most patients, we observed that three mRNA COVID-19 vaccinations led to similar antibody concentrations that were obtained in healthy individuals after two vaccinations. Surprisingly, autologous transplantation for MM did not in any way hamper antibody responses to vaccination. Additionally, patients with graft versus host disease had better responses than anticipated, and patients receiving high dose chemotherapy for acute myeloid leukemia mounted potent antibody responses. Thus, patients with hematologic malignancies simply need an extra vaccination.”

Vaccination Effective in Setting of B Cell-Depleting Therapies

When three-dose schedule antibody concentrations are reached in immunocompromised patients, they are comparable to those of healthy controls after two doses, she says, adding that vaccination should not be deferred in patients with hematologic conditions during a pandemic, or in patients receiving immunochemotherapy or transplantation.

“When B cell numbers are lower than normal, and even with very low numbers of B cells, patients can mount potent antibody responses,” Dr. Hazenberg says. “In patients receiving B cell-depleting therapies, vaccination can be effective, partly because other immune cells, such as T cells, are activated.” Nevertheless, patients with absent antibody responses are at higher risk for COVID-19-related morbidity and mortality than healthy individuals.

Raising Awareness for Those Patients at Risk

A relatively small group of patients had extremely poor antibody responses, the study team observed. “It’s important to protect these individuals from infection by wearing masks and utilizing other infection prevention measures,” Dr. Hazenberg says.

Dr. Hazenberg and colleagues are investigating other immune parameters, such as T cell and natural killer (NK) cell responses, in patients with hematologic cancer. “Vaccine effectiveness studies need to be done to confirm that antibody and T cell and NK cell responses in our patients are associated with protection against severe COVID-19 and COVID-19-related death,” she notes. “For patients who, despite vaccination, cannot be protected, it is important to develop alternatives, such as passive vaccination and post-exposure prophylaxis through monoclonal antibodies or convalescent plasma. Finally, it is crucial to continue to raise awareness for those patients who remain at risk.”