Patients with multiple myeloma (MM) remain at increased risk of developing COVID-19 even when fully vaccinated, according to a study published in JAMA Network Open.

For this study, researchers analyzed deidentified electronic health records from 507,288 patients who had medical encounters with any of 63 health care organizations in the United States between December 1, 2020, and October 8, 2021.

All patients were fully vaccinated against SARS-CoV-2 and had no prior SARS-CoV-2 infection. The study population was split into 1182 patients diagnosed with MM and 506,106 patients without cancer.

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The study was designed to test whether fully vaccinated patients with MM had a higher risk of breakthrough SARS-CoV-2 infections than similar patients without cancer, as well as to determine differences in hospitalization rates between MM patients with and without breakthrough SARS-CoV-2 infections.

Among the 506,106 non-cancer patients, the mean age was 51.3 years, and 55.5% were women. Most patients had received the Pfizer-BioNTech vaccine (90.1%), followed by Moderna (8.5%) and Johnson & Johnson (1.4%).

Among the 1182 patients with MM, the mean age was 68 years, and 51.5% were men. Most patients (88.7%) had never achieved remission, 11.7% were in relapse, and 33.8% had monoclonal gammopathy of undetermined significance (MGUS).

In terms of cancer treatment, 60% of patients had received chemotherapy, 50.3% had received targeted therapy, 12.1% had received radiotherapy, and 26.5% had stem cell transplants.

The MM patients primarily received the Pfizer-BioNTech vaccine (77%), followed by the Moderna (22.2%) and Johnson & Johnson (8%) vaccines.

Breakthrough Infection and Hospitalization

The overall risk of breakthrough SARS-CoV-2 infection was 15.4% in the MM patients and 3.9% in the non-cancer population.

With propensity score matching for demographics, comorbidities, and other factors, patients with MM still had a higher risk of breakthrough infection than their non-cancer counterparts (hazard ratio, 1.34; 95% CI, 1.06-1.69).

Of the 187 patients with MM and breakthrough infections, 86.6% had never achieved remission, 15.5% had relapsed MM, and 34.8% had MGUS. They had received chemotherapy (64.2%), targeted therapy (54.3%), radiotherapy (11.2%), and stem cell transplants (27.8%).

The estimated probability of hospitalization was 34.4% for MM patients with a breakthrough infection and 4.5% for MM patients without an infection (hazard ratio, 15.9; 95% CI, 6.2-40.3).

The researchers acknowledged the limitations of an observational analysis based on electronic medical records. However, they also noted that the broad nature of the medical record database allowed them to monitor the risks and outcomes of breakthrough SARS-CoV-2 infections in patients with MM.

“These findings raise consideration for the development and implementation of enhanced mitigation strategies and the need for studies to evaluate the timing and impact of vaccine boosters in this unique, immunosuppressed population,” the researchers wrote.


Wang L, Berger NA, Xu R. Risks of SARS-CoV-2 breakthrough infection and hospitalization in fully vaccinated patients with multiple myeloma. JAMA Netw Open. Published online November 23, 2021. doi:10.1001/jamanetworkopen.2021.37575