In myeloma, achievement of very good partial response (VGPR) post-transplant is associated with prolonged overall (OS) and progression-free survival (PFS). In this study of bortezomib, pegylated liposomal doxorubicin, and dexamethasone (VDD) in 40 patients with newly diagnosed myeloma (median follow-up 45.1 months), 2-/4-year OS estimates were 95.7%/86.5% versus 82.4%/58.2% for patients achieving ≥VGPR versus <VGPR to VDD (p=0.0241). In 30 patients undergoing transplant, PFS (p = 0.0357) and OS (p = 0.0272) were longer in patients achieving ≥VGPR to VDD. Achievement of ≥VGPR was predicted by a novel model based on occurrence after two cycles of ≥90% involved free light chain reduction, free light kappa/lambda ratio normalization, and/or ≥90% M-protein reduction. Prediction of ≥VGPR was associated with superior PFS and OS in patients with transplant. These findings emphasize the importance of achieving ≥VGPR to initial therapy, associated with prolonged OS. The predictive model provides a potential basis for developing individualized therapy, which requires further study.