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Deepening responses associated with improved progression-free survival with ixazomib versus placebo as posttransplant maintenance in multiple myeloma.

  • Goldschmidt, Hartmut1
  • Dimopoulos, Meletios A2
  • Rajkumar, S Vincent3
  • Weisel, Katja C4
  • Moreau, Philippe5
  • Chng, Wee-Joo6, 7
  • Mikala, Gábor8
  • Cavo, Michele9
  • Ramasamy, Karthik10
  • Suryanarayan, Kaveri11
  • Teng, Zhaoyang11, 12
  • Labotka, Richard11
  • Mateos, Maria Victoria13
  • 1 Internal Medicine V and National Center for Tumor Diseases (NCT), University Clinic Heidelberg, Heidelberg, Germany. [email protected] , (Germany)
  • 2 Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. , (Greece)
  • 3 Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
  • 4 Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. , (Germany)
  • 5 Department of Hematology, University Hospital Hôtel Dieu, University of Nantes, Nantes, France. , (France)
  • 6 Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore. , (Singapore)
  • 7 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. , (Singapore)
  • 8 South Pest Central Hospital, National Institute for Hematology and Infectious Diseases, Budapest, Hungary. , (Hungary)
  • 9 Seràgnoli Institute of Hematology, University of Bologna, Bologna, Italy. , (Italy)
  • 10 Oxford University Hospitals, NHS Foundation Trust, Oxford Myeloma Centre for Translational Research, Oxford, UK.
  • 11 Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
  • 12 Servier Pharmaceuticals, Boston, MA, USA.
  • 13 Hematology, Hospital Universitario de Salamanca, University Hospital of Salamanca, IBSAL, CIC, IBMCC (USAL-CSIC), Salamanca, Spain. , (Spain)
Published Article
Springer Nature
Publication Date
Nov 01, 2020
DOI: 10.1038/s41375-020-0819-8
PMID: 32327729


In the TOURMALINE-MM3 study, post-autologous stem cell transplantation maintenance therapy with the oral proteasome inhibitor ixazomib versus placebo significantly improved progression-free survival (PFS), with a favorable safety profile. With ixazomib versus placebo maintenance, deepening responses occurred in 139/302 (46%) versus 60/187 (32%) patients with very good partial response or partial response (VGPR/PR) at study entry (relative risk 1.41, P = 0.004), and median time to best confirmed deepened response was 19.9 versus 30.8 months (24-month rate: 54.2 versus 41.4%; hazard ratio (HR): 1.384; P = 0.0342). Median PFS in patients with VGPR/PR at study entry was 26.2 versus 18.5 months (HR: 0.636, P < 0.001) with ixazomib versus placebo; in a pooled analysis across arms, in patients with versus without deepening responses, the median PFS was not reached versus 15.9 months (HR: 0.245, P < 0.001). In patients with deepening responses, 24-month PFS rate was 77.4 versus 68.3% with ixazomib versus placebo (HR: 0.831; P = 0.466); in patients without deepening responses, median PFS was 17.9 versus 14.1 months (HR: 0.741; P = 0.028). These analyses demonstrate the significantly higher rate of deepening responses with ixazomib versus placebo maintenance and the association between deepening response and prolonged PFS.

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