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

摘要

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 center dot 4% with a clinical benefit rate of 71 center dot 8%. The median progression-free survival was 13 center dot 8 months [95% confidence interval (CI) 8 center dot 2-22 center dot 2] and median overall survival was not reached. The median time to best response and duration of response was 3 center dot 7 months (95% CI 2 center dot 8-10 center dot 5) and 18 center dot 4 months (95% CI 10 center dot 2-31 center dot 0) respectively. Prior immunomodulatory drug (IMID) exposure was associated with a lower ORR (40% vs. 73 center dot 7%, P = 0 center dot 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 center dot 7% and 20 center dot 6% of patients respectively. ITd dose reductions were required in 15 center dot 4%, 48 center dot 7% and 35 center dot 9% of patients respectively. The present study demonstrates promising effectiveness and tolerability of ITd as an affordable all-oral PI-IMID approach for RRMM.