OBJECTIVES : Patients with multiple myeloma after failure of immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) experience poor outcomes (Kumar SK et al. Leukemia 2017). Multiple therapies are approved for this indication; however, data from head-to-head randomized trials are not available. Indirect cross-trial assessments can provide a comparison of effectiveness, but require a common comparator. We generated ‘virtual trials’ to determine the effectiveness of EPd versus Pano-Vd or daratumumab monotherapy in patients with RRMM who received a prior IMiD and PI.

METHODS : Unanchored MAIC analyses were performed using individual patient data (IPD) from the EPd arm of ELOQUENT-3 (NCT02654132; database lock, November 2018) and summary data from the single-arm PANORAMA-2 trial of Pano-Vd (NCT01083602) and pomalidomide-naive patients from pooled daratumumab monotherapy trials (GEN501, NCT00574288; SIRIUS, NCT01985126), after aligning inclusion/exclusion criteria. IPD from ELOQUENT-3 were re-weighted to match relevant baseline summary statistics reported for PANORAMA-2 and GEN501/SIRIUS; treatment outcomes were compared across balanced trial populations. Hazard ratios (HR) were estimated using Cox regression.

RESULTS : Patients refractory to bortezomib in ELOQUENT-3 (n=38) were matched to those receiving Pano-Vd (n=55) using nine covariates. Daratumumab-naive patients from ELOQUENT-3 (n=59) were matched to those receiving daratumumab (n=66) using ten covariates. EPd showed a 48% and 54% reduction in the risk of progression/death versus Pano-Vd (median progression-free survival [PFS] 8.9 versus 5.4 months; HR=0.52 [95% CI 0.26-1.06], p=0.07) and daratumumab (median PFS 10.3 versus 4.1 months; HR=0.46 [95% CI 0.26-0.82], p=0.01), respectively. EPd showed a trend towards increased overall survival (OS) versus Pano-Vd (HR=0.42 [95% CI 0.17-1.03], p=0.06) and daratumumab (HR=0.55 [95% CI 0.19-1.60], p=0.27).

CONCLUSIONS : These statistical analyses, while limited by small effective sample sizes, suggest EPd may be associated with a longer PFS than Pano-Vd and daratumumab in patients with RRMM who received a prior IMiD and PI. OS data showed a trend favoring EPd versus Pano-Vd and daratumumab.