Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), With or Without Daratumumab in Relapsed Multiple Myeloma.

BackgroundProteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies form the backbone of initial treatment for myeloma and play an important role in the treatment of relapsed disease. However, global access to many novel therapies is limited and alkylating agents remain relevant in certain clinical settings. Ixazomib is an oral PI that enables development of all oral regimens.PatientsWe designed this open-label, multi-arm phase 2 study to evaluate the safety and efficacy of weekly oral ixazomib in various combinations for patients with relapsed MM. Herein, we discuss the results of Arms D (ixazomib, cyclophosphamide, and dexamethasone-ICd, n=33) and E (Daratumumab-ICd, n=24) that examined the ixazomib and dexamethasone in combination with cyclophosphamide or cyclophosphamide and daratumumab, respectively.ResultsThe overall response rate was 73% and 75% and ≥VGPR rate was 45% and 54% in the Arms D and E, respectively. After the median follow-up of 27 months for Arm D and 41 months for Arm E, the median progression free survival was 27.1 months (95% confidence interval [CI]: 17.8-38.6) and 37.7 months (95% CI: 17.9-NA) for the arms D and E, respectively. The median overall survival was not reached for either arm. A grade 3 or higher hematological adverse event considered at least possibly related, occurred in approximately 75% of patients.ConclusionsThe results of this phase 2 trial demonstrate clinically meaningful efficacy of ICd (±) daratumumab in the relapsed setting, with the indirect comparison suggesting a deeper response and longer PFS with adding daratumumab.