Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma.

• Type of Material: Article
• Authors: Amrita Krishnan, City of Hope; Prashant Kapoor, Mayo Clinic; Joycelynne Palmer, City of Hope; Ni-Chun Tsai, City of Hope; Shaji Kumar, Mayo Clinic; Sagar Lonial, Emory University; Myo Htut, City of Hope; Chatchada Karanes, City of Hope; Nitya Nathwani, City of Hope; Michael Rosenzweig, City of Hope; Firoozeh Sahebi, Southern California Kaiser Permanente Bone Marrow Transplant Program; George Somlo, City of Hope; Lupe Duarte, City of Hope; James F. Sanchez, City of Hope; Daniel Auclair, Multiple Myeloma Research Foundation; Stephen J. Forman, City of Hope; Jesus G. Berdeja, Sarah Cannon Research Institute
• Language: English
• Date: 2017-12-18
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/leu.2017.352
• Title of Journal or Parent Work: Leukemia
• ISSN: 0887-6924
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll 3 additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ⩾partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ⩾stable disease. The most common adverse events (⩾grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.352.