Daratumumab or Elotuzumab Plus Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma: An Indirect Comparison Based on Reconstructing Individual Patient Data from Kaplan-Meier Overall Survival Curves Using an Artificial-Intelligence Algorithm

Background: Despite advances in frontline therapy, most patients with relapsed or refractory multiple myeloma (RRMM) eventually progress, and optimal sequencing of monoclonal antibody–based regimens remains uncertain. Daratumumab and elotuzumab, each combined with lenalidomide and dexamethasone (SOC), have demonstrated overall survival (OS) benefits in randomized controlled trials. However, no head-to-head comparison exists. This study indirectly compared these regimens using reconstructed individual patient data (IPD) derived from published Kaplan–Meier curves. Materials and Methods: A literature search identified randomized trials evaluating daratumumab-SOC or elotuzumab-SOC versus SOC alone. Digitized OS curves from POLLUX and ELOQUENT-2 were processed using the IPDfromKM artificial-intelligence algorithm to reconstruct patient-level datasets. After assessing heterogeneity between SOC arms, pooled control data were used to conduct indirect comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Reconstructed HRs closely matched published trial estimates for daratumumab (0.787 vs 0.73) and elotuzumab (0.845 vs 0.82). SOC arms differed significantly between trials, with POLLUX controls demonstrating better outcomes than ELOQUENT-2 controls. In the indirect comparison using pooled SOC outcomes from the two trials, daratumumab-SOC significantly improved OS versus SOC alone (HR 0.64; 95% CI 0.52–0.78), while elotuzumab-SOC did not (HR 1.08; 95% CI 0.91–1.29). The head-to-head indirect comparison favored daratumumab over elotuzumab (HR 0.59; 95% CI 0.45–0.77). Conclusions: AI-assisted reconstruction of IPD enabled an indirect comparison of daratumumab- and elotuzumab-based triple regimens in RRMM. Results suggest superior OS for daratumumab-SOC compared with elotuzumab-SOC, supporting daratumumab as the preferred monoclonal antibody partner to lenalidomide-dexamethasone when selecting third-agent therapy for RRMM.