PMID- 35159058 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220219 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 3 DP - 2022 Feb 4 TI - The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study. LID - 10.3390/cancers14030791 [doi] LID - 791 AB - Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients < 65 vs. >/= 65 years, and for those with lymphocyte counts >/= 1000/microL vs. < 1000/microL or lactate dehydrogenase ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL. FAU - Zijlstra, Josee M AU - Zijlstra JM AUID- ORCID: 0000-0003-1074-5922 AD - Department of Hematology, Amsterdam UMC, Cancer Center, Vrije Universiteit, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. FAU - Follows, George AU - Follows G AD - Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK. FAU - Casasnovas, Rene-Olivier AU - Casasnovas RO AUID- ORCID: 0000-0002-1156-8983 AD - Department of Hematology, University Hospital F. Mitterrand and INSERM 1231, 21000 Dijon, France. FAU - Vermaat, Joost S P AU - Vermaat JSP AUID- ORCID: 0000-0002-1628-6256 AD - Department of Hematology, Leiden University Medical Center, Albinesdreef 2, 2333 ZA Leiden, The Netherlands. FAU - Kalakonda, Nagesh AU - Kalakonda N AD - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK. FAU - Choquet, Sylvain AU - Choquet S AD - Hematology, Hopital Pitie Salpetriere, 47-83 Bd de l'Hopital, 75013 Paris, France. FAU - Hill, Brian AU - Hill B AD - Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA. FAU - Thieblemont, Catherine AU - Thieblemont C AD - Hemato-Oncology, APHP, Saint-Louis Hospital & Paris University, 75010 Paris, France. FAU - Cavallo, Federica AU - Cavallo F AUID- ORCID: 0000-0003-2047-1099 AD - Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino/AOU, Citta della Salute e della Scienza di Torino, 10126 Torino, Italy. FAU - Cruz, Fatima De la AU - Cruz F AD - Hospital Universitario Virgen del Rocio, E-41013 Sevilla, Spain. FAU - Kuruvilla, John AU - Kuruvilla J AD - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada. FAU - Hamad, Nada AU - Hamad N AD - Department of Hematology, St. Vincent's Hospital Sydney, Darlinghurst, NSW 2010, Australia. AD - St Vincent's Clinical School Sydney, University of New South Wales, Sydney, NSW 2052, Australia. AD - School of Medicine, University of Notre Dame Australia, Fremantle, WA 6160, Australia. FAU - Jaeger, Ulrich AU - Jaeger U AD - Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. FAU - Caimi, Paolo AU - Caimi P AD - Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. FAU - Gurion, Ronit AU - Gurion R AD - Hematology Institute, Davidoff Center, Rabin Medical Center, Petach Tikva & Tel-Aviv University, Tel-Aviv 49100, Israel. FAU - Warzocha, Krzysztof AU - Warzocha K AD - Department of Hematology, Instytut Hematologii I Transfuzjologii, Chocimska 5, 00-791 Warsaw, Poland. FAU - Bakhshi, Sameer AU - Bakhshi S AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India. FAU - Sancho, Juan-Manuel AU - Sancho JM AUID- ORCID: 0000-0001-7168-6538 AD - Clinical Hermatology Department, Hospital Germans Trias i Pujol, Institut Catala d'Oncologia, Universitat Autonoma de Barcelona, 08916 Badalona, Spain. FAU - Schuster, Michael AU - Schuster M AD - Stony Brook Cancer Center, Stony Brook University Hospital, Stony Brook, NY 11794, USA. FAU - Egyed, Miklos AU - Egyed M AD - Department of Hematology, Teaching Hospital Mor Kaposi, Tallian Gy. U 20-32, H-7400 Kaposvar, Hungary. FAU - Offner, Fritz AU - Offner F AD - Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium. FAU - Vassilakopoulos, Theodoros P AU - Vassilakopoulos TP AD - Department of Hematology, National and Kapodistrian University of Athens, 15772 Athens, Greece. FAU - Samal, Priyanka AU - Samal P AD - Hematology-Hemato-Oncology, Institute of Medical Sciences & SUM Hospital, Bhubaneswar 751003, India. FAU - Ku, Matthew AU - Ku M AD - Department of Haematology, St.Vincent's Hospital, University of Melbourne, Melbourne, VIC 3065, Australia. FAU - Xu, Jenny AU - Xu J AD - Karyopharm Therapeutics, Newton, MA 02459, USA. FAU - Corona, Kelly AU - Corona K AD - Karyopharm Therapeutics, Newton, MA 02459, USA. FAU - Chamoun, Kamal AU - Chamoun K AD - Karyopharm Therapeutics, Newton, MA 02459, USA. FAU - Shah, Jatin AU - Shah J AD - Karyopharm Therapeutics, Newton, MA 02459, USA. FAU - Canales, Miguel AU - Canales M AD - Department of Hematology, Autonoma University, La Paz University Hospital, 28046 Madrid, Spain. FAU - Maerevoet, Marie AU - Maerevoet M AD - Department of Hematology, Institut Jules Bordet, 1070 Brussels, Belgium. LA - eng PT - Journal Article DEP - 20220204 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC8834328 OTO - NOTNLM OT - SADAL study OT - diffuse large B-cell lymphoma OT - exportin 1 OT - selinexor COIS- G.F. reports advisory boards/lecturing for Karyopharm, Roche, Abbvie, Janssen, and AstraZeneca. R-O.C. reports advisory boards for Roche, Takeda, Bristol-Myers Squibb, Amgen, Gilead, Merck, Abbvie, and research grants from Roche and Gilead outside the submitted work. C.T. reports advisory boards for Novartis, Kite Pharma, Roche, Bristol-Myers Squibb, Amgen, Gilead, Merck, Abbvie and Incyte. J.K. reports research funding from Janssen, Roche, and AstraZeneca; honoraria from Amgen, Antengene, AstraZeneca, Bristol-Myers Squibb, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics, and TG Therapeutics; consulting for Abbvie, Bristol-Myers Squibb, Gilead, Karyopharm, Merck, Roche, and Seattle Genetics; and serving on a data safety and monitoring board for Karyopharm. N.H. reports advisory boards for Novartis, Gilead, Roche, Janssen, CSL, and Antegen. U.J. reports honoraria for advisory boards for Karyopharm. P.F.C. reports research funding from ADC Therapeutics; grants from Genentech; consulting from ADC Therapeutics, Kite Pharma, Verastem Oncology, Seattle Genetics, Amgen and TG Therapeutics; and speaker's bureau from Celgene. R.G. reports consulting for Roche, Jansen, Takeda, Gilead, Medison, Novartis and Neopharm. M.S. reports personal fees from Karyopharm during the conduct of the study, and personal fees from Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Genentech, and Seattle Genetics, outside the submitted work. T.P.V. reports research support from Merck, Takeda, Amgen, Pfizer, and Dr. Reddy's; honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Amgen, Glaxo, Abbvie, Integris, and Astra Zeneca; and serves on the scientific advisory board of Takeda, Roche, Genesis Pharma, and Novartis. M.C. reports speaking for Amgen, Janssen, Novartis, Roche, Sandoz, and Takeda; advisory boards/consulting for Bristol-Myers Squibb/Celgene, Gilead/Kite Pharma, iQone, Janssen, Karyopharm, Novartis, Roche, and Sandoz; CME support, travel and accommodation from Gilead/Kite Pharma, Janssen, Novartis, Roche, and Sandoz. J.X., K.C. (Kelly Corona), K.C. (Kamal Chamoun), and J.S. are employees and stockholders of Karyopharm Therapeutics. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/02/16 06:00 MHDA- 2022/02/16 06:01 PMCR- 2022/02/04 CRDT- 2022/02/15 01:04 PHST- 2021/12/21 00:00 [received] PHST- 2022/01/24 00:00 [revised] PHST- 2022/01/25 00:00 [accepted] PHST- 2022/02/15 01:04 [entrez] PHST- 2022/02/16 06:00 [pubmed] PHST- 2022/02/16 06:01 [medline] PHST- 2022/02/04 00:00 [pmc-release] AID - cancers14030791 [pii] AID - cancers-14-00791 [pii] AID - 10.3390/cancers14030791 [doi] PST - epublish SO - Cancers (Basel). 2022 Feb 4;14(3):791. doi: 10.3390/cancers14030791.