Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US

Faith Davies, NYU Langone Health, New York, NY, USA. faith.davies@nyulangone.org.Follow
Robert Rifkin, Rocky Mountain Cancer Centers, Denver, CO, USA.
Caitlin Costello, Moores Cancer Center, University of California, San Diego, CA, USA.Follow
Gareth Morgan, NYU Langone Health, New York, NY, USA.
Saad Usmani, Carolinas Healthcare System, Charlotte, NC, USA.
Rafat Abonour, Indiana University, Indianapolis, IN, USA.Follow
Antonio Palumbo, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Dorothy Romanus, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Roman Hajek, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Evangelos Terpos, University of Athens School of Medicine, Athens, Greece.
Dasha Cherepanov, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Dawn Marie Stull, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Hui Huang, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Xavier Leleu, CHU la Miletrie, Poiters, France.
Jesus Berdeja, Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.Follow
Hans C. Lee, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Katja Weisel, Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Michael Thompson, Advocate Aurora HealthFollow
Mario Boccadoro, Azienda Ospedaliera Citta della Salute e della Scienza, Torino, Italy.Follow
Jeffrey Zonder, Karmanos Cancer Institute, Detroit, MI, USA.
Gordon Cook, Leeds Teaching Hospitals NHS Trust, Leeds, UK.Follow
Noemi Puig, Salamanca University Hospital, Salamanca, Spain.
Jorge Vela-Ojeda, Hospital de Especialidades Centro Medico Nacional la Raza, Mexico City, Mexico.
Eileen Farrelly, Xcenda, Palm Harbor, FL, USA.
Aditya Raju, Xcenda, Palm Harbor, FL, USA.
Marlo Blazer, Xcenda, Palm Harbor, FL, USA.
Ajai Chari, Icahn School of Medicine at Mount Sinai, New York, NY, USA.Follow

Affiliations

Aurora Cancer Center

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.

Type

Article

PubMed ID

33970288

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