OBJECTIVES : Multiple pomalidomide/dexamethasone-based triplet therapies have been assessed for patients with relapsed/refractory multiple myeloma (RRMM), but data from head-to-head randomized trials are not available. Indirect cross-trial assessments can provide a comparison of effectiveness, but are influenced by differing patient populations. We generated ‘virtual trials’ to determine the effectiveness of pomalidomide/dexamethasone in combination with elotuzumab (EPd), carfilzomib (KPd), or daratumumab (DPd) in RRMM.

METHODS : Unanchored matching-adjusted indirect comparison (MAIC) analyses (Signorovitch 2010) were performed using individual patient data (IPD) from the EPd arm of ELOQUENT-3 (NCT02654132) and summary data from single-arm trials of KPd (NCT01464034) and DPd (EQUULEUS, NCT01998971). IPD from ELOQUENT-3 were re-weighted to match those baseline summary statistics reported for KPd and DPd; treatment outcomes were then compared across balanced trial populations. Hazard ratios (HR) were estimated using Cox regression.

RESULTS : Patients receiving EPd (effective sample: n=44/60) were matched to those receiving KPd (n=32) using time since diagnosis, prior transplant, and refractoriness to both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). Patients receiving EPd (effective sample: n=54/60) were matched to those receiving DPd (n=103) using cytogenetic risk profile, prior lines of therapy, and refractoriness to both PIs and IMiDs. Median progression-free survival (PFS) was numerically higher for EPd versus KPd (10.3 versus 7.3 months, HR=0.671 [95% CI 0.44–1.03], p=0.08) and similar for EPd versus DPd (10.3 versus 9.9 months, HR=0.946 [95% CI 0.63–1.41], p=0.80), although differences were not statistically significant. Sensitivity analyses matching fewer or more variables produced similar findings.

CONCLUSIONS : This MAIC analysis suggests EPd may be associated with a numerically higher PFS than KPd and a similar PFS to DPd. Relative overall survival will be assessed when long-term survival data are available. These statistical based findings, matching patient characteristics that were available for each trial, are limited by small sample sizes and should be further confirmed by clinical research.