For patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible, bortezomib-melphalan-prednisone (VMP) demonstrated superior efficacy based on the VISTA trial. In subsequent trials, twice-weekly bortezomib was limited to the first cycle or completely replaced with once-weekly bortezomib to reduce toxicity. Following a systematic literature review, the efficacy and safety of modified VMP schedules (pooled data from the once-weekly bortezomib VMP arm of the GIMEMA trial and the VMP arm of the ALCYONE trial) were compared to the VISTA schedule using naive and unanchored matching-adjusted indirect comparison (MAIC). Median progression-free survival was similar between VISTA and modified VMP (20.7 months [95% CI, 18.4-24.3] vs 19.6 months [95% CI, 18.8-21.0]). Peripheral neuropathy was significantly reduced with modified VMP versus VISTA VMP (all grades: naive, 32.1% vs 46.8% and MAIC, 32.1% vs 46.7%; both p < .0001). These findings support a modified VMP dosing schedule for patients with NDMM who are transplant ineligible.