Toxicities and reasons for discontinuing TPO-RA therapy
No patients experienced adverse events related to TPO-RA therapy that were gradable by the Common Terminology Criteria for Adverse Events version 522. Three patients experienced self-resolving thrombocytosis within 4 weeks of TPO-RA initiation (platelet count 527,000-1036,000/μL) without thromboembolic events. In eight patients (53%), the TPO-RA was discontinued due to a decreased platelet transfusion requirement or otherwise adequate clinical response defined by their provider. In six patients (40%), the TPO-RA was discontinued due to death that was unrelated to TPO-RA in all cases (Table 2) . For Patient 1, eltrombopag was discontinued in the setting of grade 4 hyperbilirubinemia, thought to be related to multiple infections, hemochromatosis secondary to transfusions, autoimmune hemolytic anemia, and possible graft versus host disease. While eltrombopag and its metabolites have been reported to positively interfere with spectrophotometric measurements of total bilirubin,23,24 bilirubin continued to rise in this patient following discontinuation of eltrombopag, further supporting that the hyperbilirubinemia was unrelated to eltrombopag.
There were no new grade 3 or higher bleeding complications during TPO-RA therapy. However, four patients with pre-existing bleeding (bronchopulmonary hemorrhage, lower gastrointestinal hemorrhage, and epistaxis) experienced persistence or recurrence of these conditions while receiving a TPO-RA (Table 3).