TY - JOUR
T1 - Integrated safety profile of selinexor in multiple myeloma
T2 - experience from 437 patients enrolled in clinical trials
AU - Gavriatopoulou, Maria
AU - Chari, Ajai
AU - Chen, Christine
AU - Bahlis, Nizar
AU - Vogl, Dan T.
AU - Jakubowiak, Andrzej
AU - Dingli, David
AU - Cornell, Robert F.
AU - Hofmeister, Craig C.
AU - Siegel, David
AU - Berdeja, Jesus G.
AU - Reece, Donna
AU - White, Darrell
AU - Lentzsch, Suzanne
AU - Gasparetto, Cristina
AU - Huff, Carol Ann
AU - Jagannath, Sundar
AU - Baz, Rachid
AU - Nooka, Ajay K.
AU - Richter, Joshua
AU - Abonour, Rafat
AU - Parker, Terri L.
AU - Yee, Andrew J.
AU - Moreau, Philippe
AU - Lonial, Sagar
AU - Tuchman, Sascha
AU - Weisel, Katja C.
AU - Mohty, Mohamad
AU - Choquet, Sylvain
AU - Unger, T. J.
AU - Li, Kai
AU - Chai, Yi
AU - Li, Lingling
AU - Shah, Jatin
AU - Shacham, Sharon
AU - Kauffman, Michael G.
AU - Dimopoulos, Meletios Athanasios
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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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U2 - 10.1038/s41375-020-0756-6
DO - 10.1038/s41375-020-0756-6
M3 - Article
C2 - 32094461
AN - SCOPUS:85079825933
SN - 0887-6924
VL - 34
SP - 2430
EP - 2440
JO - Leukemia
JF - Leukemia
IS - 9
ER -