Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders

Abstract

ABSTRACT Introduction: Ixazomib is a new, orally administered, reversible proteasome inhibitor which is under investigation for the treatment of refractory/relapsed multiple myeloma (MM), systemic light chain amyloidosis (AL) and Waldenström macroglobulinemia (WM). Areas covered: This article covers the mechanism of action, pharmacology and clinical trial results of ixazomib while under investigation for the treatment of various lymphoproliferative disorders. We examine the findings from several phase 3 clinical trials (i) the pivotal TOURMALINE-MM1 study investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone; (ii) the TOURMALINE-MM3 study investigating ixazomib versus placebo as a maintenance therapy in newly diagnosed MM following induction therapy and autologous stem cell transplantation; (iii) the TOURMALINE-MM2 study investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM; and (iv) TOURMALINE-AL1 investigating ixazomib plus dexamethasone in patients with relapsed/refractory AL amyloidosis. Finally, we explore early phase clinical studies of this agent in Waldenström macroglobulinemia. Expert opinion: A key advantage of ixazomib is that it could allow an efficacious treatment approach to MM and other lymphoproliferative disorders through a convenient oral administration route. Ixazomib could soon be used in combination treatment regimens, but more work is necessary to define the place of this agent going forward. Trial registration: ClinicalTrials.gov identifier: NCT02420847. Trial registration: ClinicalTrials.gov identifier: NCT00932698. Trial registration: ClinicalTrials.gov identifier: NCT00963820. Trial registration: ClinicalTrials.gov identifier: NCT00963820. Trial registration: ClinicalTrials.gov identifier: NCT01383928. Trial registration: ClinicalTrials.gov identifier: NCT01939899. Trial registration: ClinicalTrials.gov identifier: NCT02898259. Trial registration: ClinicalTrials.gov identifier: NCT03323151. Trial registration: ClinicalTrials.gov identifier: NCT02632396. Trial registration: ClinicalTrials.gov identifier: NCT03547700. Trial registration: ClinicalTrials.gov identifier: NCT00893464. Trial registration: ClinicalTrials.gov identifier: NCT02158975. Trial registration: ClinicalTrials.gov identifier: NCT02481310. Trial registration: ClinicalTrials.gov identifier: NCT02339922. Trial registration: ClinicalTrials.gov identifier: NCT01318902. Trial registration: ClinicalTrials.gov identifier: NCT01659658. Trial registration: ClinicalTrials.gov identifier: NCT02400437.