About this item:

307 Views | 244 Downloads

Author Notes:

Corresponding Author: Amrita Krishnan, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, akrishnan@coh.org , Phone: 626-256-4673 ext. 82405, Fax: 626-301-8256

Authorship Contributions: Conception and design: AK, JP, SF, JB

Collection and assembly of data: AK, PK, JP, NT, SK, SL, MH, CK, NN, MR, FS, GS, LP, JB

Data analysis and interpretation: AS, JP, NT, LP, JS, DA

Manuscript writing: All authors

Final approval of manuscript: All authors

Dr. Krishnan serves on the speakers' bureau for Janssen, Celgene, Takeda, and Onyx, is a consultant for Janssen and Celgene, and has stock ownership in Celgene.

Dr. Kapoor is a principal investigator on studies funded by Takeda, Celgene, and Amgen. Dr. Kumar has participated in advisory boards for Takeda, Celgene, Amgen, Janssen, Abbvie, Merck and SkylineDX and receives clinical trial funding from Takeda, Janssen, Abbvie, Merck, Celgene, Sanofi, Roche, and Sanofi.

Dr. Lonial is a consultant for Millennium, Celgene, Novartis, BMS, Onyx and Janssen. Dr. Karanes has research funding than Celgene.

Dr. Rosenzweig serves on the speakers' bureau for Celgene.

Dr. Somlo serves on the speakers' bureau for Takeda, is a consultant for Pfizer, AstraZeneca, Abbvie, Puma, Novartis, and Celgene, and receives research support from Merck, Celgene, and Genentech.

Dr. Forman has license agreements with and receives research support from Mustang Therapeutics, Inc. Dr. Berdeja has received institutional funding from Takeda, Teva, Celgene, Acetylon, MEI, BMS, Amgen, Janssen, Novartis, Abbvie, Curis, Array, Consellation, and Bluebird Bio.

This work has been presented in part at the 2016 Annual Meeting of The American Society of Clinical Oncology in Chicago, IL, and the 2016 Annual Meeting of the American Society of Hematology in San Diego, CA.

The authors thank all of the research participants and their families, the Briskin family, the Multiple Myeloma Research Foundation, and the physicians, study nurses, research associates, and protocol staff at all participating sites.

Subjects:

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

Show all authors Show less authors

Tools:

Journal Title:

Leukemia

Publisher:

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2017 Macmillan Publishers Limited. All rights reserved.

Export to EndNote