Population pharmacokinetic/pharmacodynamic joint modeling of ixazomib efficacy and safety using data from the pivotal phase III TOURMALINE-MM1 study in multiple myeloma patients.

ABSTRACT: Ixazomib is an oral proteasome inhibitor approved in combination with lenalidomide and dexamethasone for the treatment of relapsed/refractory multiple myeloma (MM). Approval in the United States, Europe, and additional countries was based on results from the phase III TOURMALINE-MM1 (C16010) study. Here, joint population pharmacokinetic/pharmacodynamic time-to-event (TTE) and discrete time Markov models were developed to describe key safety (rash and diarrhea events, and platelet counts) and efficacy (myeloma protein [M-protein] and progression-free survival [PFS]) outcomes observed in TOURMALINE-MM1. Models reliably described observed safety and efficacy results; prior immunomodulatory drug therapy and race were significant covariates for diarrhea and rash events, respectively, whereas M-

SUBMITTER: Srimani JK 

PROVIDER: S-EPMC9381907 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature