Pilot Study On A Response-Directed Switch From Nilotinib To Imatinib In Newly Diagnosed Chronic Myeloid Leukemia

Context: The frontline treatment of chronic phase (CP) chronic myeloid leukemia (CML) with nilotinib has resulted in a higher rate of major molecular response (MMR) and complete cytogenetic response (CCyR) at 12 months compared to imatinib but at a higher cumulative cost and increased risk of serious adverse events. A treatment strategy aimed at maintaining long-term efficacy while minimizing both toxicities and costs is needed. Objective: The aim of the study is to evaluate the efficacy and safety of a response-directed switch from nilotinib to imatinib in patients newly diagnosed with CP-CML. Design: This is a single-center, prospective, pilot phase 2 open-label study including adult patients newly diagnosed with CP-CML screened and treated at the American University of Beirut Medical Center in Lebanon. Interventions: Patients were treated with nilotinib 300 mg orally twice daily for 12 months, and those who achieved CCyR were shifted to imatinib 400 mg orally daily, with regular follow-ups at 3, 6, 12 months, and then every 6 months thereafter. Main Outcome Measures: The primary endpoint was to evaluate the efficacy of imatinib in maintaining cytogenetic and molecular responses achieved at 12 months after nilotinib treatment in at least 85% of patients. Results: Thirteen patients were enrolled in the study. Eleven patients completed one year of nilotinib and switched to imatinib 400 mg daily as per protocol. At 3 months, all patients achieved complete hematologic response, with 7 (54%) patients having early molecular response. At 12 months, all patients achieved CCyR, of whom 5 (45%) and 4 (36%) patients achieved MMR and MR4.5, respectively. Three (27%) patients switched back to nilotinib after 18, 24, and 51 months, respectively: one patient lost CCyR after 18 months, and two patients were imatinib-intolerant. After a median follow-up of 60 months, all patients (n=12) were alive and in MMR, 6 (50%) of them in continuous MR4.5. No new safety concerns emerged in the study. Conclusions: These findings suggest that a response-directed switch from nilotinib to imatinib at 12 months is capable of maintaining long-term CCyR, with manageable side effects. This approach warrants further exploration with larger prospective trials.