Fully Vaccinated Patients With MM at Greater Risk for Breakthrough COVID-19 Infection

Patients with multiple myeloma (MM) who have been fully vaccinated against COVID-19 were found to have an increased risk of breakthrough infections and related hospitalizations, signaling the need for more studies and precautions.

Fully vaccinated patients with multiple myeloma (MM) may be at an increased risk of breakthrough COVID-19 infections and hospitalization associated with breakthrough infection compared with patients without cancer, according to findings og a recent study.

The pattern established in the cohort study, which was published in JAMA Network Open, remained even after the investigators conducted propensity score matching for demographics, adverse socioeconomic determinants of health, transplant surgeries, comorbidities, types of vaccine, and medications (HR, 1.34; 95% CI, 1.06-1.69).

“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,” wrote the investigators.

Data from the beginning of the pandemic when vaccines were unavailable had showed an increased risk of COVID-19 infection and severe outcomes among patients with MM. Although recent studies showed a low rate of seroconversion after patients with MM and other hematological malignant neoplasms received a messenger RNA vaccine against COVID-19, the risk and outcomes of breakthrough infections among the vaccinated MM population are unknown.

The investigators used the TriNetX Analytics network platform to obtain patient electronic health records (EHRs) from 63 health care organizations in the United States, containing data on 507,288 patients, 1182 of whom had MM. The patients had to have a medical encounter with a health care organization since December 1, 2020; have evidence of full vaccination between December 1, 2020, and October 8, 2022; and have no history of COVID-19 infection.

The mean (SD) age was 68.0 (11.6) years for the MM group and 51.3 (20.8) years for the noncancer group. About 60% of the entire cohort was White. Among the patients with MM, 33.8% had monoclonal gammopathy of undetermined significance (MGUS), 11.7% were in relapse, 88.7% had never been in remission, 60.0% received chemotherapy, 50.3% received targeted therapy, 12.1% had radiation therapy, and 26.6% had received stem cell transplants.

The overall risk of breakthrough infection was 15.4% in the MM population compared with 3.9% in the noncancer population. The estimated probability of hospitalization by October 8, 2021, was 34.4% for the 181 patients with MM who had a breakthrough infection, significantly higher than that for a group of matched patients without cancer and without a breakthrough infection (4.5%; HR, 15.9; 95% CI, 6.2-40.3).

Among the patients with MM who experienced a breakthrough infection, 34.8% had MGUS, 15.5% were in relapse, 86.6% had never achieved remission, 64.2% had chemotherapy, 54.3% had targeted therapy, 11.2% had radiation therapy, and 27.8% had a stem cell transplant.

“Despite the limitations inherent to observational analysis based on patient EHRs, our study leveraged a federated nationwide and real-time patient EHR database that allowed us to electronically monitor the risks and outcomes of vaccine breakthrough infections in a real-world vulnerable population,” the investigators noted.


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. 2021;4(11):e2137575. doi:10.1001/jamanetworkopen.2021.37575

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