A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16-02 trial

Br J Haematol. 2021 Aug;194(3):580-586. doi: 10.1111/bjh.17504. Epub 2021 May 15.

Abstract

We evaluated the efficacy and tolerability of continuous ixazomib-thalidomide-dexamethasone (ITd: 4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly). A total of 39 patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years with one to three prior lines of therapy were enrolled from two tertiary centres in Victoria and South Australia, Australia. The overall response rate (ORR) was 56·4% with a clinical benefit rate of 71·8%. The median progression-free survival was 13·8 months [95% confidence interval (CI) 8·2-22·2] and median overall survival was not reached. The median time to best response and duration of response was 3·7 months (95% CI 2·8-10·5) and 18·4 months (95% CI 10·2-31·0) respectively. Prior immunomodulatory drug (IMID) exposure was associated with a lower ORR (40% vs. 73·7%, P = 0·03). Survival outcomes in patients with prior proteasome inhibitor (PI) and/or IMID exposure were similar. Patients received a median (range) of 11 (1-31) cycles of therapy and six patients (15%) remained on therapy at the time of final analysis. Grade 3/4 haematological and non-haematological adverse events were reported in 7·7% and 20·6% of patients respectively. ITd dose reductions were required in 15·4%, 48·7% and 35·9% of patients respectively. The present study demonstrates promising effectiveness and tolerability of ITd as an affordable all-oral PI-IMID approach for RRMM.

Keywords: clinical trial; dexamethasone; ixazomib; myeloma; thalidomide.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Boron Compounds
  • Thalidomide
  • ixazomib
  • Dexamethasone
  • Glycine