Phase 2 study of all-oral ixazomib, cyclophosphamide and low-dose dexamethasone for relapsed/refractory multiple myeloma

There is a need for efficacious, convenient treatments with long-term tolerability for patients with relapsed/refractory multiple myeloma (RRMM). This phase 2 study evaluated the all-oral combination of ixazomib, cyclophosphamide and dexamethasone (ICd). Patients with RRMM received ixazomib 4 mg and cyclophosphamide 300 mg/m(2) on days 1, 8 and 15, and dexamethasone 40 mg on days 1, 8, 15 and 22 in 28-day cycles. The primary endpoint was overall response rate (ORR). Seventy-eight patients were enrolled (median age 63 center dot 5 years). At data cut-off, patients had received a median of 12 treatment cycles; 31% remained on treatment. ORR was 48% [16% very good partial response or better (>= VGPR)]. ORR was 64% and 32% in patients aged >= 65 and <65 years (25% and 16% >= VGPR), respectively. At a median follow-up of 15 center dot 2 months, median progression-free survival (PFS) was 14 center dot 2 months, with a trend towards better PFS in patients aged >= 65 years vs. <65 years (median 18 center dot 7 months vs. 12 center dot 0 months; hazard ratio 0 center dot 62, P = 0 center dot 14). ICd was well tolerated. The most common treatment-emergent adverse events were diarrhoea (33%), nausea (24%), upper respiratory tract infection (24%), and thrombocytopenia (22%); 10 patients (13%) had peripheral neuropathy (one grade 3). This study is registered at ClinicalTrials.gov (NCT02046070).