Matching-Adjusted Indirect Comparison of Daratumumab-Pomalidomide-Dexamethasone and Pomalidomide-Bortezomib-Dexamethasone in Relapsed/Refractory Multiple Myeloma.

Abstract

Background: Standard-of-care treatment for patients with multiple myeloma (MM) typically includes frontline lenalidomide until disease progression, making lenalidomide-refractoriness a challenge in relapsed/refractory MM (RRMM). Lenalidomide-sparing triplet therapies, daratumumab, pomalidomide, and dexamethasone (DPd) and pomalidomide, bortezomib, and dexamethasone (PVd), demonstrated efficacy in lenalidomide-exposed patients in the APOLLO and OPTIMISMM trials, respectively. Without head-to-head trial data, we assessed the comparative effectiveness of DPd versus PVd via matching-adjusted indirect comparison (MAIC).

Materials and methods: Using APOLLO individual patient data (IPD) and OPTIMISMM aggregate covariate data plus pseudo-IPD for outcomes, the APOLLO population was re-weighted to match OPTIMISMM aggregate baseline characteristics. Bayesian posterior distributions of DPd versus PVd for progression-free survival (PFS) and overall survival (OS) were estimated using a likelihood-weighted Bayesian Cox model with fixed weights.

Results: At baseline, APOLLO included a higher proportion of patients who received ≥ 2 prior lines of therapy, were refractory to prior therapies, and had advanced International Staging System stage versus OPTIMISMM, which would otherwise disadvantage APOLLO versus OPTIMISMM. The PFS hazard ratio (HR) favored DPd over PVd at 0.59 (95% credible interval [CrI]: 0.36, 0.89) with 99% probability of DPd superiority versus PVd. The OS HR appeared to favor DPd over PVd at 0.80 (95% CrI: 0.45, 1.30), with 83% probability of DPd superiority versus PVd; however, the estimated OS benefit was not conclusive.

Conclusion: This analysis suggests that DPd improves PFS and might improve OS versus PVd in patients with RRMM. Additional evidence from head-to-head trials or real-world patient databases are warranted to confirm these results.