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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gavriatopoulou, M; Chari, A; Chen, C; Bahlis, N; Vogl, DT; Jakubowiak, A; Dingli, D; Cornell, RF; Hofmeister, CC; Siegel, D; Berdeja, JG; Reece, D; White, D; Lentzsch, S; Gasparetto, C; Huff, CA; Jagannath, S; Baz, R; Nooka, AK; Richter, J; Abonour, R; Parker, TL; Yee, AJ; Moreau, P; Lonial, S; Tuchman, S; Weisel, KC; Mohty, M; Choquet, S; Unger, TJ; Li, K; Chai, Y; Li, L; Shah, J; Shacham, S; Kauffman, MG; Dimopoulos, MA

Published Date

  • September 2020

Published In

Volume / Issue

  • 34 / 9

Start / End Page

  • 2430 - 2440

PubMed ID

  • 32094461

Pubmed Central ID

  • PMC7449872

Electronic International Standard Serial Number (EISSN)

  • 1476-5551

Digital Object Identifier (DOI)

  • 10.1038/s41375-020-0756-6

Language

  • eng

Conference Location

  • England