Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma

Abstract

Introduction: The phase 3 APOLLO study demonstrated significantly better progression-free survival (PFS) and clinical responses with daratumumab, pomalidomide, and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM). On the basis of these results and those from the phase 1b EQUULEUS trial, D-Pd was approved in this patient population. In the absence of head-to-head data comparing D-Pd with further standard of care (SOC) therapies, indirect treatment comparisons (ITCs) can provide important information to help optimize treatment selection. The objective of this study was to indirectly compare PFS improvement with D-Pd versus daratumumab, bortezomib, and dexamethasone (D-Vd) and D-Pd versus bortezomib and dexamethasone (Vd) in patients with RRMM.

Methods: Patient-level data were from APOLLO, EQUULEUS, and CASTOR. Three methods of adjusting imbalances in baseline characteristics including stabilized inverse probability of treatment weighting (sIPTW), cardinality matching (CM), and propensity score matching (PSM) were initially considered. CM offers mathematically guaranteed largest matched sample meeting pre-specified maximum standardized mean difference criteria for matching covariates. sIPTW and PSM were based on propensity scores derived from logistic regression. Feasibility assessment of the PSM method returned too low effective sample size to support a meaningful comparison. CM was chosen as the base case and sIPTW as a sensitivity analysis.

Results: After harmonized eligibility criteria were applied, 253, 104, and 122 patients from the D-Pd, D-Vd, and Vd cohorts, respectively, were included in the ITC analyses. Some imbalances in baseline characteristics were identified between D-Pd and D-Vd/Vd cohorts that remained after adjustment. PFS hazard ratios showed significant improvement for D-Pd over D-Vd and Vd for CM and sIPTW analyses.

Conclusions: Results showed consistent PFS benefit for D-Pd versus D-Vd and Vd regardless of the adjustment technique used. These findings support the use of D-Pd versus D-Vd or Vd in patients with difficult-to-treat RRMM.

Trial registration: NCT03180736; NCT02136134, NCT01998971.

Keywords: Daratumumab; Indirect treatment comparison; Multiple myeloma.

© 2022. The Author(s).

Figures

Fig. 1

Progression-free survival for D-Pd versus D-Vd a prior to harmonized exclusion criteria and b after harmonized exclusion criteria. CI confidence interval, D-Pd daratumumab, pomalidomide, and dexamethasone, D-Vd daratumumab, bortezomib, and dexamethasone, HR hazard ratio

Fig. 2

Progression-free survival for D-Pd versus Vd a prior to harmonized exclusion criteria and b after harmonized exclusion criteria. CI confidence interval, D-Pd daratumumab, pomalidomide, and dexamethasone, HR hazard ratio, Vd bortezomib and dexamethasone

Fig. 3

Progression-free survival (cardinality matching). a D-Pd versus D-Vd and b D-Pd versus Vd. CI confidence interval, D-Pd daratumumab, pomalidomide, and dexamethasone, D-Vd daratumumab, bortezomib, and dexamethasone, HR hazard ratio, Vd bortezomib and dexamethasone

Fig. 4

Progression-free survival (sIPTW adjusted). a D-Pd versus D-Vd and b D-Pd versus Vd. CI confidence interval, D-Pd daratumumab, pomalidomide, and dexamethasone, D-Vd daratumumab, bortezomib, and dexamethasone, HR hazard ratio, sIPTW stabilized inverse probability of treatment weighting, Vd bortezomib and dexamethasone

Fig. 5

Progression-free survival. Values less than 1 favor D-Pd. CI confidence interval, CM cardinality matching, D-Pd daratumumab, pomalidomide, and dexamethasone, D-Vd daratumumab, bortezomib, and dexamethasone, ESS effective sample size, HR hazard ratio, sIPTW stabilized inverse probability of treatment weighting, Vd bortezomib and dexamethasone