Patients With Multiple Myeloma At Increased Risk of Breakthrough COVID-19 Infection


The overall risk of SARS-CoV-2 breakthrough infection was 15.4% in the multiple myeloma population and 3.9% in the noncancer population.

Rong Xu, PhD

Rong Xu, PhD

During the time in the COVID-19 pandemic when vaccines were not available, data show that patients with multiple myeloma were at an increased risk for COVID-19 infection and subsequent severe outcomes.

However, despite this knowledge, the risk and outcomes of SARS-CoV-2 breakthrough infection in patients with multiple myeloma who are vaccinated for COVID-19 is still unknown.

As a result, new research found that patients with multiple myeloma were at an increased risk of breakthrough infections and breakthrough infections had an association with an increased risk for hospitalization.


Led by Nathan A. Berger, MD, Center for Science, Health, and Society, Case Western University and Rong Xu, PhD, Center for Artificial Intelligence in Drug Discovery, Case Western University, investigators used the TriNetX Analytics network platform to access patients electronic health records (EHRs) from 63 healthcare organizations in the United States.

A total of 507,288 patients made up the study population. The inclusion criteria including a recent medical encounter with health care organizations since December 2020, documented evidence of full vaccination in EHRs between December 2020 - October 2021, and had no prior COVID-19 infection.

The investigators set out to test if fully vaccinated patients with multiple myeloma had a higher risk for breakthrough infections, compared to individuals without cancer. They performed propensity score matching for demographics, adverse socioeconomic determinants of health, transplant procedures, comorbidities, vaccine types, and medications.

Berger and Xu used Kaplan-Meier analysis in order to estimate the probability of breakthrough infection starting 14 days after full vaccination. Additionally, comparisons between the study cohorts occurred using Cox proportional hazards model and hazard ratio.

They tested if rates of hospitalization differed between patients with multiple myeloma with breakthrough infection, as well as propensity score-matching patients with multiple myeloma without breakthrough infection.


Data on patient characteristics show a total of 1182 fully vaccinated patients in the multiple myeloma group, with a mean age of 68.0 years compared to 506,106 patients without cancer, with a mean age of 51.3 years (P < .001).

Out of the total vaccinated patients with multiple myeloma, the study noted that 33.8% had monoclonal gammopathy of undetermined significance (MGUS), 11.7% were in relapse, and 88.7% had never achieved remission.

Further, 60.0% of patients had chemotherapy, 50.3% had targeted therapy, 12.1% had radiation therapy, and 26.5% had stem cell transplant. The mean blood lymphocyte count was 2.08 × 109/L (12.2 × 109/L).

Investigators noted the overall risk of SARS-CoV-2 breakthrough infection was 15.4% in the multiple myeloma population and 3.9% in the non-cancer population.

Then, following propensity score matching, patients with multiple myeloma remained at a significantly increased risk for breakthrough infections compared with matched patients without cancer (HR, 1.34; 95% CI, 1.06 - 1.69).

At the end of the study period in October 2021, the estimated probability of hospitalization was 34.4% for patients with multiple myeloma with breakthroughs, compared with 4.5% for matched patients without breakthroughs (HR, 15.9; 95% CI, 6.2 - 40.3).


“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,” investigators wrote.

The study, “Risks of SARS-CoV-2 Breakthrough Infection and Hospitalization in Fully Vaccinated Patients With Multiple Myeloma,” was published by JAMA Network Open.

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