BOSTON—Since early in the COVID-19 pandemic, physicians have been aware of the greater risk posed by the SARS-CoV-2 virus to patients with compromised immune systems. Among patients with multiple myeloma (MM), more than 30% died of the virus in early waves before the vaccine was available. Since the vaccination rollout, studies have shown that these patients have a less-robust response to immunization and continue to experience a greater risk of breakthrough infection and severe disease.
A team of researchers from the VA Boston Healthcare System and the VA Palo Alto, CA, Healthcare System led by Nathanael Fillmore, PhD, of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, sought to determine whether patients with MM and monoclonal gammopathy of undetermined significance (MGUS), another plasma-cell disorder, continued to have elevated risk of breakthrough infection and severe disease after receiving their first booster.1
In a presentation at the 64th American Society of Hematology Annual Meeting held Dec. 10-13 in New Orleans, Fillmore discussed the results of their retrospective cohort study in veterans. For each day of the study, each new fully vaccinated and boosted veteran with MM or MGUS was matched by age, race, VA facility, and rurality with a vaccinated and boosted patient without MM or MGUS. The primary outcomes for PCR or antigen-confirmed COVID-19 infection and the secondary outcome were confirmed infection within -1 to 14 days of documented oxygen saturation of less than 94% or use of supplemental oxygen. Pairs were followed until infection, death, or end of the study.
The analysis included 1,822 patients with MM and 6,971 with MGUS, all fully boosted with an mRNA-based vaccine. Of those, 1,706 MM patients and 6,503 MGUS patients were matched to controls. Median follow-up time was 260 days for veterans with MM and 225 for veterans with MGUS.
Patients with MM had more than 2½ times the risk of breakthrough infection following the initial booster (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.96‐3.45, p<0.001), while veterans with MGUS had slightly less than twice the risk of breakthrough infection (HR 1.90, 95% CI 1.60‐2.25, p<0.001). Veterans with MM also had more than twice the risk of severed COVID-19 disease (HR 2.39, 95% CI 1.33‐4.29, p=0.003), while patients with MGUS did not have increased risk (HR 1.06, 95% CI 0.75-1.51, p=0.74).
The team found that veterans who received their booster within 90 days of their last therapy had the greatest risk of breakthrough infection, particularly highest among those who received CD38 therapy. All groups experienced an increased incidence of breakthrough infections 3.5 months after boosting.
“Effectiveness may be reduced in patients with plasma cell disorders, likely owing to a co-existing immunosuppression due to disease process as well as associated therapy, which impacts humoral immune response,” the team reported. “Our findings suggest these vulnerable populations should be considered for additional mitigation strategies, such as pre-exposure prophylaxis, even after vaccination and boosting.”
- Fillmore NR, La J, Wu JTY, Branch-Elliman W, Monach P, Brophy M, Do NV, Munshi NC. Increased COVID-19 Breakthrough Infection Risk after Sars-Cov-2 Vaccine Boosting in Patients with Plasma Cell Disorders: A Large Nationwide Veterans Affairs Study. 2022 Nov 15;140:4297–8.
