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).