All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma

Research output: Contribution to journalArticle

Abstract

Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.

Details

Authors
  • Meletios A. Dimopoulos
  • Sebastian Grosicki
  • Wiesław W. Jędrzejczak
  • Hareth Nahi
  • Astrid Gruber
  • Markus Hansson
  • Neeraj Gupta
  • Catriona Byrne
  • Richard Labotka
  • Zhaoyang Teng
  • Huyuan Yang
  • Norbert Grzasko
  • Shaji Kumar
Organisations
External organisations
  • National and Kapodistrian University of Athens
  • Medical University of Silesia
  • Medical University of Warsaw
  • Karolinska University Hospital
  • Skåne University Hospital
  • Takeda Oncology Inc.
  • Medical University of Lublin
  • Mayo Clinic Minnesota
  • St. John of Dukla Cancer Center in Lublin
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Elderly, Multiple myeloma, Newly diagnosed, Oral therapy, Transplant-ineligible
Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalEuropean Journal of Cancer
Volume106
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes