Abstract
Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum’s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.
Highlights
Antonio Palumbo was affiliated with Millennium Pharmaceuticals, Inc., at the time this research was conducted
Due to small sample sizes, adjusted analyses were not performed for either backbone (Rd or Pd) for patients receiving therapy in earlier line of therapy (LOT) (LOTs 2–3). This is the first large database analysis evaluating the comparative effectiveness of the proteasome inhibitors (PIs) agents available for patients with refractory multiple myeloma (RRMM) in combination with either Rd or Pd backbones vs monoclonal antibody agent, daratumumab-based triplet therapy in a general population from a real-world dataset
A lower proportion of patients selected for either VRd or VPd compared to other agents in combination with Rd or Pd backbones had previous exposure to both a PI and an IMID or refractory status to both classes of drugs
Summary
Antonio Palumbo was affiliated with Millennium Pharmaceuticals, Inc., at the time this research was conducted. Marlo Blazer was affiliated with Xcenda at the time this research was conducted. This study has been presented, in part, at the European Hematology Association (EHA) 24th Congress; Amsterdam, The Netherlands; June 13–16, 2019. Extended author information available on the last page of the article. Multiple myeloma (MM) is the second most common hematologic malignancy, with an estimated incidence of 32,000 cases and 13,000 deaths in 2019 in the United States (US) [1]. Recent treatment advances in MM have led to an increased overall survival rate; the majority of MM patients require subsequent treatment for relapsed and/or refractory multiple myeloma (RRMM) [2, 3].
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