AbstractIn the phase 2 GRIFFIN trial (ClinicalTrials.gov identifier: NCT02874742), daratumumab added to lenalidomide, bortezomib, and dexamethasone (D‐RVd) improved depth of response and progression‐free survival (PFS) versus lenalidomide, bortezomib, and dexamethasone (RVd) alone in transplant‐eligible (TE) patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient‐reported outcomes (PROs) collected using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30‐item (QLQ‐C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module 20‐item (QLQ‐MY20), and EuroQol 5‐Dimension 5‐Level (EQ‐5D‐5L) tools on day 1 of cycles 1, 2, and 3; on day 21 of cycle 4 (end of induction therapy); on day 1 of cycle 5; on day 21 of cycle 6 (end of posttransplant consolidation therapy); and at months 6, 12, 18, and 24 of maintenance therapy. Meaningful improvements from baseline were seen in most of the PRO scales with both treatments after consolidation and were sustained for at least 2 years of maintenance treatment. Large reductions from baseline (~20 points) were especially observed in pain symptoms for both treatment groups, although these were numerically higher for patients receiving D‐RVd during the majority of the time points. In addition, improvements in key scales, such as global health status, fatigue symptoms, and physical functioning, were also seen with both D‐RVd and RVd. These improvements in health‐related quality of life contribute to the totality of evidence supporting the improvement in clinical outcomes such as response rates and PFS with D‐RVd in induction, consolidation, and maintenance therapy in TE patients with NDMM.