Older Patients With Myeloma May Have Suboptimal Response to COVID-19 Vaccination

According to a study published in Blood, older patients with multiple myeloma (MM) experienced reduced efficacy with BNT162b2, Pfizer/BioNTech’s COVID-19 vaccine. However, certain factors identified patients who had a higher probability of immune response to vaccination, such as normalized immunoglobulins.

Lead study author Evangelos Terpos, MD, PhD, of the National and Kapodistrian University of Athens in Greece, told ASH Clinical News that given their immunocompromised state, patients with MM have a higher risk of infection. This risk is further complicated by advanced age and the presence of comorbidities. Approximately 77% of patients with MM who develop COVID-19 tend to progress to moderate to severe acute respiratory dysfunction, and 8% of these cases lead to critical condition.

Previous data have shown that more than 80% of patients with MM and COVID-19 are admitted to the hospital, and nearly one-third of these hospitalized patients are at risk of death. Currently authorized COVID-19 vaccines, as well as emerging vaccines and therapeutic options, are protective against infection, but the data regarding the efficacy of these approaches in MM are sparse.

In this study, Dr. Terpos and colleagues examined the efficacy of BNT162b2 in 48 patients with MM. Another 104 age- and sex-matched volunteers served as controls.

Researchers collected serum from patients and controls on day one, prior to the first vaccine dose, and again on day 22, prior to the second dose. The investigators measured neutralizing antibodies (NAbs) against SARS-CoV-2 in the serum each time.

The median age across both groups was 83 years. The investigators noted that the age of this population was driven higher by a Greek COVID-19 immunization initiative which prioritized older patients and health care workers.

At the time of inoculation, approximately 72.9% of patients with MM were receiving anti-myeloma therapy. Four patients were in remission after previous therapy and were not receiving MM-directed therapy at time of vaccination. Another nine patients had smoldering myeloma.

On day one, the investigators did not observe NAb titers of 30% or more, the cutoff value that defined positivity, in either patients or controls. There was also no difference in NAb titers between patients with MM versus controls on day one.

On day 22 after the first vaccine dose, patients with MM had significantly lower NAb titers compared with the control group (median = 20.6% vs. 32.5%, respectively; p<0.01). In addition, just 25% of patients with MM developed NAb titers of 30% or more after the first dose, compared with 54.8% of controls. In contrast, a total of four patients with MM who were in remission developed NAb titers of ≥50%, defined as clinically relevant viral inhibition, while 20.2% of controls developed NAb titers of ≥50%. The four patients in remission had normal uninvolved immunoglobulin levels following treatment.

One patient with smoldering myeloma had demonstrated NAb titers of 30% or more, while NAb titers at this level were observed in 11 of the patients with active MM (28.2%). The investigators noted that this patient demonstrated normal uninvolved immunoglobulin levels, whereas the other eight patients with smoldering myeloma showed immunoparesis in at least one uninvolved immunoglobulin.

This study is limited by its small size. Dr. Terpos said the results require confirmation in a larger patient population, as those findings may impact the clinical care of patients with MM. “Additionally, we need to know when to do the vaccination while the patients are on therapy and what to do in nonresponders to vaccination,” he said. “Do we need to offer them a third vaccine shot, or do we need to treat them with a prophylactic dose of immunoglobulins against the novel coronavirus?”

The authors declare no relevant conflicts of interest.


Terpos E, Trougakos IP, Gavriatopoulou M, et al. Low neutralizing antibody responses against SARS-CoV-2 in elderly myeloma patients after the first BNT162b2 vaccine dose [published online ahead of print, 2021 Apr 16] Blood. doi: 10.1182/blood.2021011904.

The present study shows that patients with MM seem to mount a less effective immune response to vaccination against COVID-19. To some degree this is unsurprising, but it is good to see this relationship objectively documented by studies like this.

The study is limited in the number of patients that were tested, so conclusions about the efficacy of the vaccine in the various stages of the disease, as well as in the context of ongoing therapy, remain elusive. For instance, do patients with monoclonal gammopathy but no therapy, particularly those with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma, mount an effective immune response? I would imagine they do. On the other hand, patients receiving intense anti-myeloma treatments like monoclonal antibodies, proteasome inhibitors, or stem cell transplant may be less likely to mount that response. Lastly, it would be interesting to know if patients with prior vaccination and effective antibody titers lose them as a consequence of myeloma therapy.

Despite the findings reported here, I think all my loved ones and patients should be vaccinated. As we learn more regarding immunity to the vaccination, we will be able to determine the best course of action for this patient population. Also, antibody titers are not a complete assessment of immunity against a pathogen or a vaccine. It is possible that lower titers still provide some protection or that T-cell immunity also plays a role in the process.

Because so many people in the community are getting vaccinated, people with myeloma are at a low risk of becoming infected with COVID-19. The current coronavirus pandemic is no different from many other serious human pathogens that remain in circulation, but which have already been handled through herd immunity.

Ideally, we would like to see a study in which various therapies are applied and tested for hundreds of patients with various stages of the disease. Also, it would be interesting to see results of functional T-cell assays to more thoroughly assess immunity.

Rafael Fonseca, MD
Mayo Clinic
Scottsdale, Arizona