LAUSR

In this issue of Blood , Garzon et al 1 and Kuruvilla et al 2 report on the results of phase 1 dose-escalation studies of selinexor in patients with acute myeloid leukemia (AML) and different subtypes of non-Hodgkin lymphoma (NHL), respectively. Together the studies report on 174 patients (95 with AML and 79 with NHL) treated. The drug appears to be tolerable in most patients, with mostly grade 1 or 2 adverse events. The most frequent adverse events included fatigue, anorexia, nausea, diarrhea, vomiting, and weight loss. A variety of dosing regimens were tested as described, largely in an attempt to limit the observed gastrointestinal toxicity, but none was successful, and the recommended phase 2 dosage is 60 mg flat dosing twice weekly in 4-week cycles. Pharmacokinetic studies in a cohort of patients demonstrated no dose accumulation. Grade 3 or 4 toxicities tended to be hematologic.