Safety of live-attenuated MMR vaccination in patients with multiple myeloma receiving daratumumab after autologous stem cell transplantation

Abstract

Abstract Introduction: Antibodies for vaccine-preventable infections are significantly reduced after autologous stem cell transplantation (ASCT). However, because of the risk of disseminated infection, live-attenuated vaccinations such as the measles-mumps-rubella (MMR) vaccine are contraindicated in immunocompromised patients including patients with multiple myeloma who have undergone ASCT within the prior two years or those who are receiving antibody-based treatment. As data from the PERSEUS, CASSOPEIA, SWOG 1803, and GMMG-HD7 trials matures, incorporation of anti-CD38 antibodies after ASCT may become increasingly adopted into clinical practice. MMR vaccination is especially important for these immunocompromised patients given the rising rates of vaccine hesitancy in the general population and the recent increase in confirmed measles cases in the United States. To better understand the risks of live-attenuated vaccination in immunocompromised patients, we conducted a multi-center retrospective study to evaluate the safety of MMR vaccination in patients with multiple myeloma receiving daratumumab after ASCT. Methods: Five US academic medical centers contributed data on 41 patients with myeloma who received MMR vaccination while receiving daratumumab following ASCT. Baseline characteristics were outlined by descriptive analysis. MMR vaccinations were administered at the discretion of the treating oncologist and patients received the M-M-R II formulation (Merck & Co, Inc). Vaccine titers were not checked as this is not routine practice at participating centers. Safety outcomes included adverse events following vaccination such as infectious complications, confirmed infections, rash, and general malaise. Results: Of the 41 patients included, the median age was 65 years (range 47-85), 34% of patients were non-Hispanic Black and 49% of patients were female. The median prior lines of therapy was one (range 1-3). The median immunoglobulin G (IgG) level was 482 mg/dL (range 198-1791 mg/dL) and 26% of patients were receiving IVIG supplementation at the time of vaccination. All patients received a prior ASCT at a median of 134 days before starting daratumumab. The majority of patients (59%) received daratumumab in combination with lenalidomide (52%) or pomalidomide (7%) and dexamethasone, with remaining patients receiving in combination with a proteasome inhibitor (7%) or as monotherapy (34%). Ninety-five percent of patients were receiving monthly daratumumab at the time of vaccination. The other two patients were receiving weekly daratumumab. Initial MMR vaccination was administered at a median of 22 cycles (616 days) of daratumumab following ASCT and four patients received a second dose of MMR. The median time from ASCT to MMR vaccination was 768 days. The most common adverse events were acute sinusitis (5%) and COVID-19 infection (5%) which occurred at a median of 8 days (range 6-41) after MMR vaccination. Skin rash, headache, and arthralgias were each reported in one patient post-vaccination. No patients developed an active measles, mumps, or rubella infection after vaccination. No hospitalizations or deaths were reported post-vaccination. Conclusion: Our findings suggest MMR vaccination in immunocompromised patients with myeloma receiving daratumumab after ASCT appears to be safe. Though a limited sample size, we did not observe any vaccine-related disseminated measles, mumps, or rubella infections post-vaccination. MMR vaccination is especially important for these immunocompromised patients given the rising rates of vaccine hesitancy in the general population and the increase in confirmed measles cases in the United States during 2024 and 2025.