@article{9b3220475493481d9202f7491d668bfc,
title = "A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202)",
abstract = "Preclinical studies have demonstrated activity of the oral proteasome inhibitor (PI) ixazomib (IXA) in bortezomib-resistant multiple myeloma (MM) and synergy with immunomodulatory drugs. We therefore conducted a phase I/II study to establish the safety and preliminary efficacy of IXA with pomalidomide (POM) and dexamethasone (DEX) in lenalidomide (LEN)/PI-refractory MM. Dose escalation established a 4 mg dose of POM and IXA and 20/40 mg dose of DEX as the maximum tolerated dose. The phase II portion of the trial was redesigned and started anew after six patients had been randomized to IXA-POM-DEX due to a rapidly changing treatment landscape. Among the 29 evaluable LEN/PI-refractory patients treated with IXA-POM-DEX in phase I/II, the overall response rate (partial response or better) was 51.7% with a median duration of response of 16.8 months (range 56 days to 4.1 years), median progression-free survival of 4.4 months (95% confidence interval [CI]: 3.0–18.4), and median overall survival of 34.3 months (95% CI: 19.2 to not reached). Hematologic, gastrointestinal, and constitutional adverse events were common and consistent with the side-effect profiles of the individual agents. Our results support further evaluation of this all-oral regimen in relapsed/refractory MM.",
author = "Voorhees, {Peter M.} and Suman, {Vera J.} and Tuchman, {Sascha A.} and Laubach, {Jacob P.} and Hani Hassoun and Efebera, {Yvonne A.} and Flora Mulkey and Misty Bova-Solem and Katelyn Santo and Destin Carlisle and McCarthy, {Philip L.} and Richardson, {Paul G.}",
note = "Funding Information: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233191, UG1CA233290, UG1CA233331, UG1CA233373. https://acknowledgments.alliancefound.org . It was also supported in part by funds from Celgene/BMS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: PV has served on Advisory Boards and has done consulting work with BMS/Celgene and Takeda. ST has served on Advisory Boards for BMS/Celgene. PM has done consulting work with and received honoraria from BMS/Celgene and Takeda. PM's institution, Roswell Park Comprehensive Cancer Center, has received research support from BMS/Celgene. PR has served on Advisory Boards for and received research support from BMS/Celgene and Takeda. VS, JL, HH, YE, FM, MB‐S, CS, and DC have no conflicts of interests to report. Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC.",
year = "2021",
month = dec,
day = "1",
doi = "10.1002/ajh.26361",
language = "English (US)",
volume = "96",
pages = "1595--1603",
journal = "American journal of hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "12",
}