Ponatinib-Induced Adverse Effects: Thrombocytopenia, Pancreatitis and Hepatoxicity-- A Case Report

Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease that generates from malignant transformation of pluripotent hematopoietic stem cells. First line treatment for CML is the tyrosine kinase inhibitor (TKI), imatinib. For patients resistant or intolerant to imatinib, other TKIs, dasatinib, nilotinib, and ponatinib, are approved treatments. Patients who are resistant or intolerant to other agents are started on ponatinib as a last line option. Common adverse events of ponatinib are hypertension, dry skin, rash, abdominal pain, constipation, and nausea. More serious adverse effects include cardiovascular effects, fluid retention, pancreatitis, severe myelosuppression, and hepatotoxicity. Treatment for these adverse effects can include interrupting ponatinib therapy and providing symptomatic and supportive care. Reintroduction of agent can be considered when the serious event has resolved or the potential benefit of resuming therapy is judged to outweigh the risk. The patient is a 65 year old Caucasian male with a history of imatinib-resistant CML. The patient was started on ponatinib 45mg approximately 3 months prior to presentation after failure of previous regimens. He requires platelet transfusions for ponatinib associated thrombocytopenia. He presents with 4 days of new right flank pain with radiation to his right groin. Evidence of pancreatitis was found on endoscopic retrograde cholangiopancreatography (ERCP). LFTs were elevated on admission. The patient had no history of alcohol or steroid use. Ponatinib was discontinued on admission and within three days the patient’s symptoms of thrombocytopenia, pancreatitis and hepatotoxicity began to resolve. After complete resolution of the pancreatitis, the patient was restarted on ponatanib 15mg as an outpatient. Patients started on ponatinib should have their serum lipase, amylase, liver enzymes, and platelets checked every 2 weeks for the first 2 months and then monthly. By checking levels regularly it may allow the physicians to decrease the dose before complications arise that may require hospitalization. Signs and symptoms of pancreatitis should also be monitored and started on a low dose to avoid complications