Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials
Author:
Gavriatopoulou Maria, Chari Ajai, Chen Christine, Bahlis Nizar, Vogl Dan T.ORCID, Jakubowiak Andrzej, Dingli David, Cornell Robert F., Hofmeister Craig C.ORCID, Siegel DavidORCID, Berdeja Jesus G., Reece Donna, White Darrell, Lentzsch Suzanne, Gasparetto Cristina, Huff Carol Ann, Jagannath Sundar, Baz Rachid, Nooka Ajay K.ORCID, Richter Joshua, Abonour Rafat, Parker Terri L., Yee Andrew J., Moreau Philippe, Lonial Sagar, Tuchman Sascha, Weisel Katja C., Mohty Mohamad, Choquet Sylvain, Unger T. J., Li Kai, Chai Yi, Li Lingling, Shah Jatin, Shacham Sharon, Kauffman Michael G., Dimopoulos Meletios Athanasios
Abstract
AbstractSelinexor 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.
Publisher
Springer Science and Business Media LLC
Subject
Oncology,Cancer Research,Hematology
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