Cancer Management and Research (Feb 2019)
Early and sustained deep molecular response achieved with nilotinib in high Sokal risk chronic myeloid leukemia patients
Abstract
Uzma Zaidi,1 Bushra Kaleem,2 Munira Borhany,1 Sidra Maqsood,2 Naveena Fatima,2 Gul Sufaida,3 Saqib Hussain Ansari,1 Tasneem Farzana,1 Tahir Sultan Shamsi1 1Department of Clinical Hematology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan; 2Department of Clinical Research, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan; 3Department of Molecular Medicine, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan Background: Nilotinib (Tasigna®) is a second-generation tyrosine kinase inhibitor that shows faster and deeper molecular responses (MR) in comparison to Imatinib as initial therapy in chronic phase chronic myeloid leukemia (CML). Efficacy and safety data for nilotinib in the Asian population is scarce, particularly in Pakistan. We aimed to determine the MR to nilotinib and its safety profile in patients with chronic phase CML.Patients and methods: This observational study was conducted among 173 patients with newly diagnosed CML presenting in the chronic phase. Most patients (50.1%) had a high Sokal score at diagnosis. All patients received nilotinib 600 mg/day. The hematological and molecular responses were assessed at 3 and 6 months respectively and thereafter at 6-monthly intervals. Long-term event free survival (EFS), transformation free survival (TFS), overall survival (OS) and adverse events were observed. Results: Cumulative incidence of major MR (MMR) was 86% and deep MR (DMR ie MR 4.0 and MR4.5) was 39%. Early MMR and DMR after 6 months of therapy were achieved by 74.9% and 37% of patients, respectively. Two-year EFS, TFS and OS rates for all patients were 91.9%, 92% and 92.3%, respectively. At median follow-up of 24 months, 81% and 49% of patients sustained MMR and DMR, respectively. The main adverse events were weight gain (4.6%) and abdominal pain (4%). Conclusion: This study showed promising results in terms of achievement of early and sustained DMR in chronic phase CML, therefore, we recommend nilotinib as frontline treatment in Pakistani population. Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, nilotinib, molecular response, Sokal Risk Score