TY - JOUR
T1 - Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
AU - Krishnan, Amrita
AU - Kapoor, Prashant
AU - Palmer, Joycelynne M.
AU - Tsai, Ni Chun
AU - Kumar, Shaji
AU - Lonial, Sagar
AU - Htut, Myo
AU - Karanes, Chatchada
AU - Nathwani, Nitya
AU - Rosenzweig, Michael
AU - Sahebi, Firoozeh
AU - Somlo, George
AU - Duarte, Lupe
AU - Sanchez, James F.
AU - Auclair, Daniel
AU - Forman, Stephen J.
AU - Berdeja, Jesus G.
N1 - Funding Information:
Conflict of interest 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 from 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, Constellation, and Bluebird Bio. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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 three 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 three 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.
AB - 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 three 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 three 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85042371832&partnerID=8YFLogxK
U2 - 10.1038/s41375-018-0038-8
DO - 10.1038/s41375-018-0038-8
M3 - Article
C2 - 32082000
AN - SCOPUS:85042371832
VL - 32
SP - 1567
EP - 1574
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 7
ER -