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.

Aurora Cancer Center Advocate Aurora Health Milwaukee WI USA

Azienda Ospedaliera Citta della Salute e della Scienza Torino Italy

Carolinas Healthcare System Charlotte NC USA

CHU la Miletrie Poiters France

Department of Oncology Hematology and Bone Marrow Transplantation with Section of Pneumology University Medical Center Hamburg Eppendorf Hamburg Germany

Hospital de Especialidades Centro Medico Nacional la Raza Mexico City Mexico

Icahn School of Medicine at Mount Sinai New York NY USA

Indiana University Indianapolis IN USA

Karmanos Cancer Institute Detroit MI USA

Leeds Teaching Hospitals NHS Trust Leeds UK

Millennium Pharmaceuticals Inc a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA

Moores Cancer Center University of California San Diego CA USA

NYU Langone Health New York NY USA

Rocky Mountain Cancer Centers Denver CO USA

Salamanca University Hospital Salamanca Spain

Tennessee Oncology Sarah Cannon Research Institute Nashville TN USA

University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

University of Athens School of Medicine Athens Greece

University of Texas MD Anderson Cancer Center Houston TX USA

Xcenda Palm Harbor FL USA

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