Clinical characteristics and outcomes in risk-stratified patients with smoldering multiple myeloma: data from the Czech Republic Registry of Monoclonal Gammopathies.

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma (MM). The aim of this study was to report clinical characteristics and outcomes of patients with SMM stratified based on their risk of progression to MM using the Mayo 20/2/20 criteria. Data were leveraged from the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). Key outcomes included progression-free survival from SMM diagnosis to active MM diagnosis or death (PFS), progression-free survival from SMM diagnosis to progression on first line (1 L) MM treatment or death (PFS2), and overall survival (OS). Of 498 patients, 174 (34.9%) were classified as high risk and 324 (65.1%) as non-high risk. Median follow-up was approximately 65 months. During follow-up, more patients in the high-risk vs non-high-risk group received 1 L MM treatment (76.4% vs 46.6%, p < 0.001). PFS, PFS2, and OS were significantly shorter in high-risk vs non-high-risk patients (13.2 vs 56.6 months, p < 0.001; 49.9 vs 84.9 months, p < 0.001; 93.2 vs 131.1 months, p = 0.012, respectively). The results of this study add to the growing body of evidence that patients with high-risk vs non-high-risk SMM have significantly worse outcomes, including OS.

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

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.