A phase I/II study of twice-weekly ixazomib plus pomalidomide and dexamethasone in relapsed and refractory multiple...

Triplets incorporating proteasome inhibitors, immunomodulatory drugs, and dexamethasone are active regimens for patients with relapsed/refractory multiple myeloma (RRMM). All-oral regimens may offer greater real-world feasibility and convenience than other options. This phase I/II dose-escalation and expansion study evaluated the oral proteasome inhibitor ixazomib at a dose of 3 or 4 mg on a twice-weekly schedule (days 1, 4, 8, and 11) in 21-day cycles, plus pomalidomide at a dose of 2, 3, or 4 mg (days 1-14) and dexamethasone 12 or 8 mg (days of/after ixazomib), in 50 patients with RRMM. Patients had received a median of 2 prior lines, with 98.0% and 88.0% having received prior lenalidomide and bortezomib, respectively. The highest dose level investigated (ixazomib 4 mg, pomalidomide 4 mg) was the recommended phase II dose (RP2D). Patients received a median of 11 cycles. Common toxicities were neutropenia (76.0%; grade 3/4 22.0%/4.0%), thrombocytopenia (70.0%; 8.0%/8.0%), leukopenia (68.0%; 22.0%/0%), fatigue (52.0%; 4.0%/0%), and anemia (46.0%; 2.0%/0%). During dose escalation, two dose-limiting toxicities (grade 3 upper respiratory tract infection; grade 3 neutropenia) were reported. The overall response rate was 60.0% (24.0% ≥very good partial response [VGPR]) in all 50 patients and 65.8% (28.9% ≥VGPR) in the 38 patients who received the RP2D; the median duration of response was 18.0 and 19.3 months, median progression-free survival was 13.9 and 17.8 months, and 3-year overall survival rates were 85.2% and 80.3%, respectively. Twice-weekly ixazomib plus pomalidomide-dexamethasone is a well-tolerated, efficacious all-oral regimen with real-world utility in RRMM.