Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma

Shaji K Kumar, Francis K. Buadi, Betsy LaPlant, Alese Halvorson, Nelson Leung, Prashant Kapoor, David M Dingli, Morie Gertz, Ronald S. Go, Peter Leif Bergsagel, Yi Lin, Angela Dispenzieri, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Rafael Fonseca, Suzanne R. Hayman, Alexander Keith Stewart, John A. Lust, Joseph R MikhaelWilson Gonsalves, Craig Reeder, Tomas Skacel, S Vincent Rajkumar, Martha Lacy

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41–88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.

Original languageEnglish (US)
Article number70
JournalBlood Cancer Journal
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2018

ASJC Scopus subject areas

  • Hematology
  • Oncology

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