Tolerability and Toxicity of Nilotinib in Imatinib Resistent or Intolerant Chronic Myeloid Leukemia in Pakistani Population

Objective: To monitor the tolerability and toxicity of nilotinib therapy in imatinib resistant or intolerant CML patients. Study Design: Descriptive case series study Place and Duration of the Study: The study was conducted at Shaukat Khanum Memorial Cancer Hospital and research Center (SKMCH RC) Lahore, from December 2009 to June 2011. Materials and Methods: All eligible patients were monitored by history physical examination, electrocardiography (ECG), hematologic, electrolytes pancreatic enzymes evaluation at baseline, after 2, 5, 9 13 weeks interval. Data analyzed with SPSS v.19. Toxicity was graded according to National Cancer Institute s Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTC v3). Results: We included 33 eligible patients. Seventy percent (23) were male. Median age 37 years (range 13 – 62). The indications for nilotinib were: Twenty four patients resistant to imatinib and 9 imatinib intolerant. These were generally mild to moderate in intensity. The most frequent adverse effect was myelosupression of which lower grade (1 and 2) thrombocytopenia was commonest (57%). Second most frequent complication was hepatotoxicity. Five patients (15%) had elevation of lipase enzyme out of them 2 had grade 3/4 derangement. Fatal toxicity occurred in only one patient who developed accelerated hypertension, led to massive intracranial hemorrhage and death. None of the patients in our study had serious QT interval prolongation. Treatment was interrupted in eight patients (5 due to hematologic toxicity, one due to hepatotoxicity, one due to elevated lipase and one patient with intracranial hemorrhage). Conclusion: Nilotinib is generally a well tolerated drug with hematological toxicity being the most common treatment related adverse effect. However due to serious events like intracranial hemorrhage as in our patient and risk of sudden cardiac death, it needs frequent monitoring during treatment.