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Background  Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments.    Methods  We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs).    Results  The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection.    Conclusions  This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12885-021-08451-x.

Infection risks in multiple myeloma: a systematic review and meta-analysis of randomized trials from 2015 to 2019