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Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials.

Authors
  • Gavriatopoulou, Maria1
  • Chari, Ajai2
  • Chen, Christine3
  • Bahlis, Nizar4
  • Vogl, Dan T5
  • Jakubowiak, Andrzej6
  • Dingli, David7
  • Cornell, Robert F8
  • Hofmeister, Craig C9
  • Siegel, David10
  • Berdeja, Jesus G11
  • Reece, Donna3
  • White, Darrell12
  • Lentzsch, Suzanne13
  • Gasparetto, Cristina14
  • Huff, Carol Ann15
  • Jagannath, Sundar2
  • Baz, Rachid16
  • Nooka, Ajay K17
  • Richter, Joshua10
  • And 17 more
  • 1 Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. [email protected] , (Greece)
  • 2 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 3 Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada. , (Canada)
  • 4 Charbonneau Cancer Research Institute, Calgary, AB, Canada. , (Canada)
  • 5 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 6 University of Chicago Medical Center, Chicago, IL, USA.
  • 7 Mayo Clinic, Rochester, MN, USA.
  • 8 Vanderbilt University Medical Center, Nashville, TN, USA.
  • 9 Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH, USA.
  • 10 Department of Hematology, John Theurer Cancer Center, Hackensack, NJ, USA.
  • 11 Sarah Cannon Research Institute, Nashville, TN, USA.
  • 12 QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada. , (Canada)
  • 13 Department of Medicine, Division of Hematology/Oncology, Columbia University, New York, NY, USA.
  • 14 Duke University Cancer Center, Durham, NC, USA.
  • 15 Johns Hopkins University, Baltimore, MD, USA.
  • 16 Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. , (Mali)
  • 17 Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • 18 Indiana University Cancer Center, Indianapolis, IN, USA. , (India)
  • 19 Yale School of Medicine, New Haven, CT, USA.
  • 20 Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • 21 University of Nantes, Nantes, France. , (France)
  • 22 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
  • 23 University Medical Center of Hamburg-Eppendorf, Hamburg, Germany. , (Germany)
  • 24 Hôpital Saint Antoine, Paris, France. , (France)
  • 25 La Pitié-Salpêtrière Hospital, Paris, France. , (France)
  • 26 Karyopharm Therapeutics, Newton, MA, USA.
  • 27 Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. , (Greece)
Type
Published Article
Journal
Leukemia
Publisher
Springer Nature
Publication Date
Sep 01, 2020
Volume
34
Issue
9
Pages
2430–2440
Identifiers
DOI: 10.1038/s41375-020-0756-6
PMID: 32094461
Source
Medline
Language
English
License
Unknown

Abstract

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1-2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.

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