Study Treatment
toxicity, neutropenia, neuropathy
NEUTROPENIA, FEBRILE NEUTROPENIA, NEUROPATHY, THROMBOCYTOPENIA, APPENDIX
In this phase II single-center trial all patients received the same induction treatment. Induction treatment consisted of 6 cycles of therapy. Cycle 1 consisted of ixazomib 4 mg and dexamethasone 20 mg each given once weekly on days 1, 8, and 15 with continuous cyclophosphamide at a dose of 50 mg per day. Cycle length was 28 days with continuation of cyclophosphamide during week 4 of each cycle. If treatment was tolerated in cycle 1 (see below) patients then received ixazomib 4 mg and dexamethasone 20 mg twice weekly (on days 1, 4, 8, 11, 15, and 18) during cycles 2-6 with no change in the continuous cyclophosphamide (50 mg/day). Cycle lengths remained 28 days for the remaining 5 cycles.To proceed from once-weekly cycle 1 to twice-weekly cycles 2-6 dosing, patients could not have experienced grade ≥3 neutropenia or thrombocytopenia, febrile neutropenia, treatment related grade ≥3 non-hematology toxicity or treatment related grade ≥2 neuropathy. If any of the above were experienced, dose modifications were implemented which can be found in the Supplementary Appendix.After the completion of 6 cycles of induction therapy, patients had the option of proceeding to autologous stem cell transplantation or maintenance therapy. Patients who went on to autologous transplant came off study and were followed per schedule evaluation. Patients not going on to autologous transplant continued with maintenance therapy which consisted of ixazomib at 4 mg days 1, 8, and 15 of a 28-day cycle for 1.5 years (to complete 2 years of protocol treatment) or until relapse.