e92144f098706164ee1781b8cda8f3c4 pmc_35159058.pdf d6fe96d759628e007b34df2df768cf96b87a2538 pmc_35159058.pdf 3ca089e2680d16338e9f7921770b8d3eb4c89578862e2d9c7da9019f78aa6765 pmc_35159058.pdf Title: The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study Subject: 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/L vs. < 1000/L or lactate dehydrogenase ULN vs. > 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. Keywords: selinexor; diffuse large B-cell lymphoma; exportin 1; SADAL study Author: Josée M. Zijlstra, George Follows, Rene-Olivier Casasnovas, Joost S. P. Vermaat, Nagesh Kalakonda, Sylvain Choquet, Brian Hill, Catherine Thieblemont, Federica Cavallo, Fatima De la Cruz, John Kuruvilla, Nada Hamad, Ulrich Jaeger, Paolo Caimi, Ronit Gurion, Krzysztof Warzocha, Sameer Bakhshi, Juan-Manuel Sancho, Michael Schuster, Miklos Egyed, Fritz Offner, Theodoros P. Vassilakopoulos, Priyanka Samal, Matthew Ku, Jenny Xu, Kelly Corona, Kamal Chamoun, Jatin Shah, Miguel Canales and Marie Maerevoet Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Feb 9 09:52:21 2022 CET ModDate: Wed Feb 9 10:07:48 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1048542 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- VNUVFB+VnURWPalladioL Type 1 Custom yes yes no 10 0 YINHIN+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 NPKPFC+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 NTJCTA+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 57 0 ZSBMBZ+EURM10 Type 1 Builtin yes yes no 79 0 SNXEGL+CMSY10 Type 1 Builtin yes yes no 83 0 XIRVNA+EURB10 Type 1 Builtin yes yes no 96 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 100 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-15 02:42:51 CEST RepresentationInformation: pmc_35159058.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-02-27 18:44:19 CET Size: 1048542 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 257 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Endpoints Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Baseline Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Demographics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Duration of Selinexor Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Efficacy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Age Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Renal Function Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Germinal Center B-Cell versus Non-Germinal Center B-cell Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Absolute Lymphocyte Count Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Prior ASCT vs. Transplant Ineligible Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Prior Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Disease Refractory Status Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Ann Arbor Stage 1 or 2 vs. 3 or 4 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Lactate Dehydrogenase >ULN vs. ULN Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Safety Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study Author: Josée M. Zijlstra, George Follows, Rene-Olivier Casasnovas, Joost S. P. Vermaat, Nagesh Kalakonda, Sylvain Choquet, Brian Hill, Catherine Thieblemont, Federica Cavallo, Fatima De la Cruz, John Kuruvilla, Nada Hamad, Ulrich Jaeger, Paolo Caimi, Ronit Gurion, Krzysztof Warzocha, Sameer Bakhshi, Juan-Manuel Sancho, Michael Schuster, Miklos Egyed, Fritz Offner, Theodoros P. Vassilakopoulos, Priyanka Samal, Matthew Ku, Jenny Xu, Kelly Corona, Kamal Chamoun, Jatin Shah, Miguel Canales and Marie Maerevoet Subject: 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/L vs. < 1000/L or lactate dehydrogenase ULN vs. > 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. 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