@article{3f0aa0fcecde4baf9d879454464eba36,
title = "Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results",
abstract = "Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0–14·7). Progression-free survival was 4·6 months (range, 0·4–17·3). Grade 3–4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3–4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.",
keywords = "Bruton tyrosine kinase, dexamethasone, ibrutinib, multiple myeloma",
author = "Richardson, {Paul G.} and Bensinger, {William I.} and Huff, {Carol Ann} and Costello, {Caitlin L.} and Nikoletta Lendvai and Berdeja, {Jesus G.} and Anderson, {Larry D.} and Siegel, {David S.} and Daniel Lebovic and Sundar Jagannath and Laubach, {Jacob P.} and Stockerl-Goldstein, {Keith E.} and Long Kwei and Fong Clow and Laurence Elias and Zeena Salman and Thorsten Graef and Elizabeth Bilotti and Ravi Vij",
note = "Funding Information: This study was supported by funding from Pharmacyclics LLC, an AbbVie Company and by a grant from the NIH/NCI Cancer Center Support (Grant P30 CA008748). We would like to thank Michelle Maglio, BS, of Dana-Farber Cancer Institute, funded by the RJ Corman Multiple Myeloma Research Fund, and Brian Haas, PhD, a medical writer supported by funding from Pharmacyclics LLC, an AbbVie Company, for editorial assistance to the authors during preparation of this manuscript. Funding Information: PGR has had a consultancy/advisory role with Celgene, Millenium/Takeda, Janssen, Novartis, Bristol-Meyers Squibb (BMS) and Genmab. WIB has received honoraria from Cel-gene, Amgen and Takeda; has a consultancy/advisory role from Celgene, Sanofi and BMS; has received research funding from Celgene, Sanofi, Acetylon, BMS and Takeda; has been on the speakers{\textquoteright} bureau of Celgene, Amgen and Takeda; and has provided expert testimony from Celgene and Takeda. CAH has had a consultancy/advisory role with Celgene, Glenmark, Takeda and Karyopharm; and has received research funding from Pharmacyclics LLC, an AbbVie Company, Karyopharm and Medimmune. CC has had a consultancy/advisory role with Celgene and Millennium/Takeda; has received honoraria from Celgene and Takeda; and has been on the speakers{\textquoteright} bureau from Janssen. NL has employment with Janssen and has received research funding from Millennium, Karyopharm, GlaxoSmithKline and Sanofi. JGB has received research funding from Pharmacyclics LLC, an AbbVie company, Amgen, Teva, Constellation, Vivolux, Bluebird, Takeda, Celgene, BMS, AbbVie, Janssen and Novar-tis and has travelled with BMS, Celgene and Takeda. LDA has been on the speakers{\textquoteright} bureau for Takeda, Onyx and Cel-gene. DSS has received honoraria, has had a consultancy/advisory role, and has been on the speaker{\textquoteright}s bureau for Celgene, Takeda, BMS, Amgen, Novartis and Merck. DL has received research funding from Celgene; has been on the speakers{\textquoteright} bureau for Amgen, Celgene and Takeda; and has received travel expenses from Amgen, Celgene and Takeda. SJ has received honoraria, has had a consultancy/advisory role, and has been on the speakers{\textquoteright} bureau for Celgene, Jans-sen, BMS, Medicom and Oncotracker; and has received research funding from Celgene, Janssen and BMS. JPL has received research funding from Onyx, Novartis, Celgene and Millennium. KES-G has equity ownership with Abbot and AbbVie and has been on the speakers{\textquoteright} bureau for Janssen. LK is an employee of Pharmacyclics LLC, an AbbVie Company, and has equity ownership with AbbVie and Abbott. FC has had employment from Pharmacyclics LLC, an AbbVie Company; and has equity ownership with AbbVie. LE has had employment with Pharmacyclics LLC, an AbbVie Company; and has equity ownership with AbbVie, Gilead, Ziopharm, Exelixis and Karyopharm. ZS has employment with Pharmacyclics LLC, an AbbVie Company, and has equity ownership with AbbVie. TG has employment and patents/royalties/other intellectual property with Pharma-cyclics LLC, an AbbVie Company, and has equity ownership with AbbVie. EB has employment with Pharmacyclics LLC, an Abbvie Company, and has equity ownership in AbbVie. RV has received honoraria from Takeda, Celgene, Amgen, BMS, Janssen, AbbVie, Karyopharm and Sanofi and research funding from Takeda and Amgen. Funding Information: This study was supported by funding from Pharmacyclics LLC, an AbbVie Company and by a grant from the NIH/ NCI Cancer Center Support (Grant P30 CA008748). We would like to thank Michelle Maglio, BS, of Dana-Farber Cancer Institute, funded by the RJ Corman Multiple Myeloma Research Fund, and Brian Haas, PhD, a medical writer supported by funding from Pharmacyclics LLC, an AbbVie Company, for editorial assistance to the authors during preparation of this manuscript. Publisher Copyright: {\textcopyright} 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.",
year = "2018",
month = mar,
doi = "10.1111/bjh.15058",
language = "English (US)",
volume = "180",
pages = "821--830",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "6",
}