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

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.

Fig. 1. Platelet change in patients during selinexor treatment.

a Change in platelets from baseline (cycle 1 day 1 of treatment with selinexor or a selinexor-containing regimen) through day 154 for all patients with MM. Patients were included in the graph up until the point in time when they received an intervention for thrombocytopenia (platelet transfusion, TPO receptor agonist, dose reduction, and dose interruption) and were then subsequently removed from the analysis. b Change in platelets for all patients who did not receive a platelet transfusion or TPO receptor agonist while on a selinexor trial. Patients who received a dose reduction or interruption were included in the analysis up until the point in time where they had an intervention and were subsequently removed from the analysis.

Fig. 2. Neutrophil change in patients during selinexor treatment and after a G-CSF.

a Change in neutrophils from baseline (C1D1 of treatment with selinexor or a selinexor-containing regimen) through day 154 for all patients with MM. Patients were included in the graph up until the point in time when they received an intervention for neutropenia (filgrastim/pegfilgrastim, dose reduction, and dose interruption) and were then subsequently removed from the analysis. b Change in neutrophils for all patients who received filgrastim or pegfilgrastim.