@article{499e5c8be501423a90eb9b028e0fd791,
title = "A 2:1 randomized, open-label, phase II study of selinexor vs. physician{\textquoteright}s choice in older patients with relapsed or refractory acute myeloid leukemia",
abstract = "Selinexor, a selective inhibitor of nuclear export, has demonstrated promising activity in patients with acute myeloid leukemia (AML). This randomized, phase II study evaluated selinexor 60 mg twice weekly (n = 118) vs. physician{\textquoteright}s choice (PC) treatment (n = 57) in patients aged ≥60 years with relapsed/refractory (R/R) AML. The primary outcome was overall survival (OS). Median OS did not differ significantly for selinexor vs. PC (3.2 vs. 5.6 months; HR = 1.18 [95% CI: 0.79–1.75]; p = 0.422). Complete remission (CR) plus CR with incomplete hematologic recovery trending in favor of selinexor occurred in a minority of patients. Selinexor treated patients had an increased incidence of adverse events. The most common grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anemia, hyponatremia. Despite well-balanced baseline characteristics, there were numerically higher rates of TP53 mutations, prior myelodysplastic syndrome, and lower absolute neutrophil counts in the selinexor group; warranting further investigation of selinexor in more carefully stratified R/R AML patients. Registered trial: NCT02088541.",
keywords = "AML, Selinexor, refractory, relapsed",
author = "Kendra Sweet and Bhavana Bhatnagar and Hartmut D{\"o}hner and Will Donnellan and Olga Frankfurt and Michael Heuser and Vamsi Kota and Hongtao Liu and Emmanuel Raffoux and Roboz, {Gail J.} and Christoph R{\"o}llig and Showel, {Margaret M.} and Strickland, {Stephen A.} and Susana Vives and Shijie Tang and Unger, {Thaddeus J.} and Anita Joshi and Yao Shen and Alvarez, {Mariano J.} and Andrea Califano and Marsha Crochiere and Yosef Landesman and Michael Kauffman and Jatin Shah and Sharon Shacham and Savona, {Michael R.} and Pau Montesinos",
note = "Funding Information: KS: advisory board honorarium from Astellas, Bristol-Myers Squib, Novartis, and Takeda. Consulting fees from Stemline Therapeutics. Research support from Incyte. HL: research support from Karyopharm Therapeutics Inc and Bristol-Myers Squibb advisory board honorarium from Agios Pharmaceuticals. VK: advisory board honorarium from Pfizer Inc., Novartis, Incyte. Research funding from Amgen. SSJ: advisory board honorarium from AbbVie Inc, Astellas Pharma Inc, Incyte, Jazz Pharmaceuticals, KiTE Pharma, Kura Oncology, Novartis, and Pfizer. Research support from Sunesis Pharmaceuticals. TJU, SS, MGK, ST, YL, and JS: employees and stockholders of Karyopharm Therapeutics Inc. MC: former employee and stockholder of Karyopharm Therapeutics Inc. AJ: consultant to Karyopharm Therapeutics Inc. GR: research support from Cellectis. Consultancy, advisory board or data and safety monitoring committee membership of AbbVie Inc, Actinium Pharmaceuticals Inc, Agios Pharmaceuticals, Amphivena Therapeutics, Aargenx, Array BioPharma, Astex Therapeutics, Astellas Pharma Inc, AstraZeneca, Bayer, Celgene, Celltrion, Daiichi Sankyo, Eisai Co Ltd, Epizyme, Helsinn, Janssen Pharmaceutica, Jasper Therapeutics, Jazz Pharmaceuticals, MEI Pharma, Novartis, Orsenix, Otsuka Pharmaceutical, Pfizer, Roche, Genentech, Sandoz, Takeda, and TrovaGene. MRS: research support from Astex, Incyte, Takeda, TG Therapeutics. Stockholder of Karyopharm Therapeutics Inc. Consulting or advisory board honoraria from Abbvie, BMS, Celgene, Karyopharm Therapeutics Inc, Ryvu, Sierra Oncology, Takeda, TG Therapeutics. MJA: full-time employee and equity holder at DarwinHealth, Inc. AC: personal fees and other from DarwinHealth Inc., outside the submitted work. Patent applications pending, patents 62/211,373 and 62/211,562 filed on 8/28/15 pending to Columbia University, and a patent 62/253,342 provisional filed on 11/10/15 pending to Columbia University. BB: research support from Karyopharm Therapeutics Inc and Cell Therapeutics Inc. Advisory board honoraria from Cell Therapeutics Inc, Novartis, Astellas, and Kite Pharma. WD: research support from AbbVie, Aileron Therapeutics, Astex Pharmaceuticals, AstraZeneca, Bellicum Pharmaceuticals, Bristol-Myers Squibb, Cantex Pharmaceutics, Celgene, Celularity, CTI Biopharma, Forma Therapeutics, Forty Seven Inc, Genentech, H3 Biomedicine, Incyte, Janssen, Karyopharm Therapeutics Inc, Kite Pharma, MedImmune, Onconova Therapeutics, Pfizer, PTC Therapeutics, Seattle Genetics, Stemline Therapeutics, Takeda Pharmaceuticals, and Ryvu Therapeutics. Consulting fees from AbbVie, Amgen, Seattle Genetics, and PTC Therapeutics. OF: personal fees from AbbVie, Agios, Celgene, Jazz Pharmaceuticals, Bristol-Myers Squibb, and Pfizer. HD: personal fees from AbbVie, Agios, Amgen, Astellas, Astex Pharmaceuticals, Celgene, Janssen, Jazz Pharmaceuticals, Helsinn Healthcare, Novartis, Oxford Biomedica, and Roche. Research support from Amgen, Celgene, Jazz Pharmaceuticals, Novartis, AROG Pharmaceuticals, Bristol-Myers Squibb, Pfizer, and Sunesis Pharmaceuticals. MH: honoraria from Novartis, Pfizer, prIME Oncology Inc. Consulting fees from Novartis, Pfizer, AbbVie, Bayer, Daiichi Sankyo. Research support from Novartis, Pfizer, Bayer, Daiichi Sankyo, Astellas, BerGenBio, and Roche. CR: research support from AbbVie, Amgen, Bayer, Celgene, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer, and Roche. Personal fees from AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer, and Roche. SK: advisory board honoraria from AbbVie, Celgene, Janssen, Takeda, Adaptive Biotechnologies, Kite Pharma, and MedImmune/AstraZeneca. Research support from AbbVie, Celgene, Janssen, Merck, Novartis, Roche, Sanofi, and Takeda. ER, MMS, SV, and PM: no conflict of interest. Funding Information: The authors would like to thank the patients, their families, and all investigators involved in this study. The medical writing support was provided by Minal Kotecha, Ph.D., and Liz Anfield, and editorial support by Bethany King, BSc, all of Core Medica, UK, supported by Karyopharm according to Good Publication Practice guidelines ( https://www.acpjournals.org/doi/10.7326/M15-0288 ). The sponsor was involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, the ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2021",
doi = "10.1080/10428194.2021.1950706",
language = "English (US)",
volume = "62",
pages = "3192--3203",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "13",
}
