Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib

Abstract

This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1-7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (⩾PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%.

Figure 1

Patient disposition across the entire study including addition of dexamethasone.

Figure 2

(a) Waterfall plot of the distribution of depth of the response observed for single agent ixazomib and (b) waterfall plot of the distribution of depth of the response observed across the entire study.

Figure 3

Overall survival (OS) and event-free survival (EFS) for the entire study population.

Figure 4

(a) The distribution of all grades of toxicities considered at least possibly related to the drug administration. (b) The incidence of hematological toxicity across individual cycles, highlighting lack of any cumulative hematological toxicity.