Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis

Background The role of maintenance therapy in transplant ineligible multiple myeloma (MM) patients following a period of fixed duration induction therapy remains unclear. Objectives We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) examining maintenance therapy compared to observation. Methods We conducted a comprehensive search including MEDLINE, Embase, and the Cochrane database up to February 28, 2020, for RCTs comparing maintenance therapy to observation in newly diagnosed transplant ineligible MM patients. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. We performed meta-analyses using a random-effects model and assessed certainty using GRADE methodology. Main results We included five RCTs with a total of 1139 patients. Patients receiving maintenance therapy had improved progression-free survival (PFS) compared to observation (Hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.38 to 0.62, high certainty); however, there was no difference in overall survival (HR 0.96, 95% CI 0.76-1.2, moderate certainty). Adverse events were higher in the maintenance group compared to observation (very low to moderate certainty). Conclusion Maintenance therapy increases PFS in transplant ineligible MM patients following a fixed period of induction therapy; however, this must be weighed against the increased risk of adverse events.