Indirect treatment comparison of DVRd plus DR maintenance (PERSEUS study) versus DVTd or VTd with or without lenalidomide maintenance in transplant-eligible patients with previously untreated multiple myeloma

To compare the effectiveness of induction and consolidation with daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) plus maintenance therapy with daratumumab and lenalidomide (DR) with 2 treatment regimens that are widely used for transplant-eligible newly diagnosed multiple myeloma (TE NDMM): bortezomib, thalidomide, and dexamethasone (VTd) or daratumumab-VTd (DVTd) followed by observation (Obs) or lenalidomide maintenance. Individual patient-level data from the PERSEUS (NCT03710603) and CASSIOPEIA (NCT02541383) trials were used to compare DVRd + DR with VTd + Obs and with DVTd + Obs. Inverse probability of treatment weighting was used to adjust for differences in baseline patient characteristics between the two trials; inverse probability of censoring weighting was used to adjust for the second randomization of CASSIOPEIA. Data from the CASSIOPEIA and Myeloma XI (EudraCT 2009-010956-93) trials were combined to model outcomes associated with lenalidomide (R) maintenance following induction with DVTd or VTd. DVRd + DR showed superior progression-free survival compared with DVTd + Obs (hazard ratio, 0.39 [95% CI = 0.26–0.59]), VTd + Obs (0.17 [95% CI = 0.12–0.25]), DVTd + R (0.62 [95% CI = 0.41–0.92]), and VTd + R (0.29 [95% CI = 0.18–0.43]). Sensitivity analyses showed results were consistent with the base case. The indirect treatment comparison was unanchored due to a lack of common comparators and relied on external data from the Myeloma XI trial to model outcomes associated with DVTd or VTd followed by R maintenance. Despite best efforts to identify and adjust for important treatment effect modifiers, there is a potential for residual confounding. Findings from this study suggest that DVRd followed by DR maintenance offers superior survival outcomes compared with current standards of care in TE patients with NDMM.