The COVID-19 pandemic has had an outsized impact on individuals with underlying socialand medical vulnerability, leading to increased rates of severe disease, hospitalization,and death in these groups. Participants with underlying immune compromise, such as thosewith multiple myeloma, represent one such group. The advent of vaccines againstSARS-CoV-2 has significantly limited morbidity and mortality across all groups, but theeffectiveness of vaccination in individuals who are less likely to mount sufficientantibody response is uncertain. For this reason, booster vaccines have been recommendedfor those with underlying immune compromise. However, several key gaps remain in ourunderstanding of how to best protect these individuals.There is a dearth of real-world evidence about the effectiveness of vaccination andboosters in patients who are immunocompromised, and very little information specificallyabout the recently approved mRNA boosters. Additionally, rates of vaccination and boosteruptake in the United States remain low. A rapid, decentralized method of ascertaininginformation related to booster vaccine response and adverse events related to vaccinesand COVID-19 infection is critical not only to answer questions about the boostervaccines, but to develop an infrastructure for answering similar questions about futurevaccines or other diseases.