Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma

Br J Cancer. 2019 Oct;121(9):751-757. doi: 10.1038/s41416-019-0581-8. Epub 2019 Sep 27.


Background: Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients.

Methods: Ninety patients have been included. Ixazomib-thalidomide-dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year.

Results: The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare.

Conclusions: Ixazomib-thalidomide-dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM.

Trial registration number: NCT02410694.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boron Compounds / administration & dosage
  • Boron Compounds / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Female
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives
  • Humans
  • Induction Chemotherapy
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Progression-Free Survival
  • Survival Rate
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects


  • Boron Compounds
  • Thalidomide
  • ixazomib
  • Dexamethasone
  • Glycine

Associated data

  • ClinicalTrials.gov/NCT02410694