Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1

Research output: Contribution to journalArticle


Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safety were evaluated in subgroups defined according to type (proteasome inhibitor [PI] and immunomodulatory drug) and number (1 vs. 2 or 3) of prior therapies received. Of 722 patients, 503 (70%) had received a prior PI, and 397 (55%) prior lenalidomide/thalidomide; 425 patients had received 1 prior therapy, and 297 received 2 or 3 prior therapies. At a median follow up of ~15 months, PFS was prolonged with ixazomib-Rd vs. placebo-Rd regardless of type of prior therapy received; HR 0.739 and 0.749 in PI-exposed and -naïve patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and -naïve patients, respectively. PFS benefit with ixazomib-Rd vs. placebo-Rd appeared greater in patients with 2 or 3 prior therapies (HR 0.58) and in those with 1 prior therapy without prior transplant (HR 0.60) versus those with 1 prior therapy and transplant (HR 1.23). Across all subgroups, toxicity was consistent with that seen in the intent-to-treat population. In patients with relapsed/refractory multiple myeloma, ixazomib-Rd was associated with a consistent clinical benefit vs. placebo-Rd regardless of prior treatment with bortezomib or immunomodulatory drugs. Patients with 2 or 3 prior therapies, or 1 prior therapy without transplant seemed to have greater benefit than patients with 1 prior therapy and transplant. TOURMALINE-MM1 registered at identifier: 01564537.


  • María-Victoria Mateos
  • Tamas Masszi
  • Norbert Grzasko
  • Markus Hansson
  • Irwindeep Sandhu
  • Ludek Pour
  • Luísa Viterbo
  • Sharon R Jackson
  • Anne-Marie Stoppa
  • Peter Gimsing
  • Mehdi Hamadani
  • Gabriela Borsaru
  • Deborah Berg
  • Jianchang Lin
  • Alessandra Di Bacco
  • Helgi van de Velde
  • Paul G Richardson
  • Philippe Moreau
External organisations
  • University Hospital of Salamanca
  • Semmelweis University
  • Skåne University Hospital
  • University of Alberta
  • Masaryk University
  • Instituto Português de Oncologia do Porto Francisco Gentil (IPO)
  • Institut Paoli-Calmettes
  • Copenhagen University Hospital
  • Medical College of Wisconsin
  • Takeda Oncology Inc.
  • Dana-Farber Cancer Institute
  • Nantes University Hospital
  • Medical University of Lublin
  • Middlemore Hospital
  • Colțea Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology


  • Journal Article
Original languageEnglish
Pages (from-to)1767-1775
Number of pages9
Issue number10
Publication statusPublished - 2017 Oct
Publication categoryResearch