Bortezomib-melphalan-prednisone (VMP) is an established induction regimen for transplant-ineligible newly diagnosed multiple myeloma (NDMM), yet optimal post-induction strategies remain unclear. This study evaluated the effectiveness of bortezomib maintenance following VMP using target trial emulation. We compared a prospective maintenance cohort (KMMWP-174 study) with an external control cohort from a multicenter registry. Eligible patients completed 9 VMP cycles, achieved ≥ partial response, and were progression-free for 60 days. The index date was maintenance initiation for cases and day 60 post-VMP for controls. Propensity score matching (1:1) balanced baseline covariates. The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. Sensitivity analyses included multivariable regression, landmark analyses, and E-value assessment. Among 178 eligible patients, 60 comprised the maintenance cohort and 118 the control cohort; 54 per group were analyzed after matching. Median PFS was significantly longer with bortezomib maintenance (26.5 vs. 8.8 months; HR 0.437, 95% CI: 0.275–0.694, P < 0.001). PFS benefits were consistent across subgroups, including patients aged ≥ 70 years, those with ISS stage II-III disease, and those with high-risk cytogenetics. OS showed a favorable trend (HR 0.703, P = 0.252). Grade ≥ 3 adverse events occurred in 31.4% (control) and 18.7% (maintenance). No grade ≥ 3 peripheral neuropathy was observed. Bortezomib maintenance following VMP significantly prolonged PFS in transplant-ineligible NDMM with acceptable toxicity. These real-world data support proteasome inhibitor-based maintenance where VMP remains widely used, particularly among older adults with limited treatment options.
Supplementary Information: The online version contains supplementary material available at 10.1007/s00277-026-06849-w.
Keywords: Bortezomib; Comparative effectiveness research; Maintenance chemotherapy; Multiple myeloma; Proteasome inhibitors; Target trial emulation.