An open-label, randomized phase 2 study evaluated the all-oral triplet combination of ixazomib (an orally administered proteasome inhibitor) plus cyclophosphamide (at 2 different doses) and low-dose dexamethasone (ICd) as a 12-month induction therapy in previously untreated, transplant-ineligible patients with multiple myeloma (MM); Dimopoulos and colleagues presented preliminary analysis results of the postinduction data from this trial.1
Seventy patients were randomized to receive 2 induction therapies: ixazomib (4.0 mg orally [PO] on days 1, 8, and 15) plus cyclophosphamide (PO on days 1, 8, and 15) dosed at either 300 mg/m2 (ICd-300 arm; n = 36) or 400 mg/m2 (ICd-400 arm) and dexamethasone (40 mg PO on days 1, 8, 15, and 22); patients may receive up to 13 cycles of 28-day induction therapy. After cycle 1, a safety lead-in evaluation of dose-limiting toxicities (DLTs) was performed in 6 evaluable patients; no DLTs were observed in either arm. Following induction, all patients received maintenance therapy with single-agent ixazomib 4.0 mg PO on days 1, 8, and 15 of each 28-day cycle; this therapy was repeated every 28 days until progressive disease, death, or unacceptable toxicity. At a mean follow-up of 9 cycles, the primary end point of complete response plus very good partial response rates was 28% for the ICd-300 cohort and 21% for the ICd-400 cohort; overall response rates were 78% and 65%, respectively. Grade 3/4 adverse events (AEs) (68% vs 64%), mainly neutropenia (35% vs 14%) and anemia (15% and 11%), were higher in the ICd-400 arm in comparison to the ICd-300 arm, as were rates of serious AEs (50% vs 39%), and dose reductions (21% vs 19%); treatment discontinuations were similar between the 2 arms. Higher rates of antiemetic use for AEs (50% and 39%) and granulocyte colony-stimulating factor use for AEs (53% and 11%) were also reported in the ICd-400 cohort. Four deaths were reported on the study (cardiac arrest, upper gastrointestinal hemorrhage, pneumonia). Based on these results, the authors concluded that the all-oral triplet combination of ICd-300 showed a tolerable and manageable toxicity profile, and represents a novel frontline treatment option for elderly, transplant-ineligible patients with newly diagnosed MM.
- Dimopoulos M, et al. ASH 2015. Abstract 26.