@article{f0a2d84847f94207875677ec725d1323,
title = "Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study",
abstract = "Several cytogenetic abnormalities are associated with poor outcomes in multiple myeloma (MM). We prospectively analyzed the impact of cytogenetic abnormalities on outcomes during the phase 2 PX-171-003-A1 study of single-agent carfilzomib for relapsed and refractory MM. In the response-evaluable population (257/266), fluorescence in situ hybridization (FISH)/conventional cytogenetic profiles were available for 229 patients; 62 (27.1%) had high-risk cytogenetics-del 17p13, t(4;14) or t(14;16) by interphase FISH or deletion 13 or hypodiploidy by metaphase cytogenetics-and 167 (72.9%) had standard-risk profiles. Generally, baseline characteristics were similar between the subgroups, but International Staging System stage III disease was more common in high-vs standard-risk patients (41.9% vs 27.5%) as was Eastern Cooperative Oncology Group performance status 1/2 (85.5% vs 68.3%). Overall response was comparable between the subgroups (25.8% vs 24.6%, respectively; P=0.85), while time-to-event end points showed a trend of shorter duration in high-risk patients, including median duration of response (5.6 months (95% confidence interval (CI) 3.7-7.8) vs 8.3 months (95% CI 5.6-12.3)) and overall survival (9.3 (95% CI 6.5-13.0) vs 19.0 months (95% CI 15.4-NE); P=0.0003). Taken together, these findings demonstrate that single-agent carfilzomib is efficacious and has the potential to at least partially overcome the impact of high-risk cytogenetics in heavily pre-treated patients with MM.",
keywords = "carfilzomib, cytogenetics, multiple myeloma, proteasome inhibitor, refractory, relapsed",
author = "Jakubowiak, {A. J.} and Siegel, {D. S.} and T. Martin and M. Wang and R. Vij and S. Lonial and S. Trudel and V. Kukreti and N. Bahlis and M. Alsina and A. Chanan-Khan and F. Buadi and Reu, {F. J.} and G. Somlo and J. Zonder and K. Song and Stewart, {A. K.} and E. Stadtmauer and Harrison, {B. L.} and Wong, {A. F.} and Orlowski, {R. Z.} and S. Jagannath",
note = "Funding Information: AJJ: Consultant and Advisory Boards for Celgene, Millennium, Onyx Pharmaceuticals and Bristol-Myers Squibb; honoraria from Celgene, Millennium, Bristol-Myers Squibb; speakers bureau for Celgene. DSS: Consultant, honoraria, and Board of Directors or advisory committee membership for Millennium and Celgene. TM: Honoraria from Celgene; consultant for Onyx Pharmaceuticals. MW: Research funding from Onyx Pharmaceuticals. RV: Consultant for and research funding from Onyx Pharmaceuticals. SL: Consultant for Millennium, Celgene, Novartis, Bristol-Myers Squibb, Onyx Pharmaceuticals and Merck. VK: Honoraria from Celgene, Janssen Ortho and Roche. NB: Honoraria from and speakers bureau for Celgene. MA: Consultant for Millennium and Novartis; Board of Directors or advisory committee membership for Millennium and Novartis; research funding from Millennium and Allergan. FJR: Research funding from Celgene and speakers bureau for Onyx Pharmaceuticals. GS: Advisory committee for Onyx Pharmaceuticals. JZ: Consultant for Millennium and Amgen; speakers bureau for Millennium and Celgene; research funding from Millennium; honoraria from Medtronics. AKS: Consultant for and research funding from Celgene, Millennium, Novartis, Bristol-Myers Squibb and Onyx Pharmaceuticals. ES: Consultant and speakers bureau for Celgene and Millennium. AFW: Employed by and equity ownership in Onyx Pharmaceuticals. RZO: Honoraria from and Board of Directors or advisory committee membership for Onyx Pharmaceuticals, Amgen, Array Bio-pharma, Bristol-Myers Squibb, Celgene, Janssen Pharmaceuticals, Merck and Millennium Pharmaceuticals and research funding from Bristol-Myers Squibb, Celgene and Millennium Pharmaceuticals. SJ: Honoraria for Millennium, Celgene, Onyx Pharmaceuticals and Merck; Board of Directors or advisory committee membership for Ortho Biotech, Imedex, Medicom World Wide, OptumHealth Education and PER Group. The other authors declare no conflict of interest. Funding Information: We thank all patients who contributed to this study and their families. Thanks are also due to the investigators and staff from the additional participating study sites. We would like to acknowledge all the participating research nurses and data coordinators. The clinical operations lead for the study was Jessica Taylor (Onyx Pharmaceuticals, Inc.), statistical support was provided by Yu-Lin Chang, Sandra Dixon, MS and Mei Huang, MS (Onyx Pharmaceuticals, Inc) and critical review of the manuscript for scientific accuracy was undertaken by Thomas Renau, PhD, A. Peter Morello III, PhD, CMPP and Edward Kavalerchik, MD (Onyx Pharmaceuticals, Inc.). Medical writing and editing services were provided by Brian E. Szente, PhD and Michael Raffin from Fishawack Communications (North Wales, PA) and supported by funding from Onyx Pharmaceuticals, Inc. and the Multiple Myeloma Research Consortium. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2013",
month = dec,
doi = "10.1038/leu.2013.152",
language = "English (US)",
volume = "27",
pages = "2351--2356",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "12",
}