Abstract
Background: Achieving complete cytogenetic response (CCyR) at 12 months for patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib as first line, is associated with significantly improved progression-free survival. Nilotinib has shown a faster and higher rate of CCyR and molecular response as compared to imatinib. However, nilotinib use is associated with diet restriction, higher financial costs, and its long-term use is incriminated in cardiovascular and metabolic complications.
Methods: In this prospective single center trial, we evaluated the ability of imatinib to maintain a CCyR achieved after 12 months of first-line treatment with nilotinib. Inclusion criteria were adult patients with previously untreated Philadelphia -positive CML in chronic phase, with a WHO performance status ≤ 2. Patients received 1-year treatment with nilotinib (300mg twice daily) then were shifted to imatinib 400mg daily.
Results: Eleven patients (5 females) were so far enrolled in the study, with a median age at diagnosis of 50 years (range 31-83). Patients were started on Nilotinib at a median of 29 days (range 2-32) from diagnosis. One patient had to discontinue nilotinib after 6 months and start dasatinib due to recurrent pancreatitis that resolved upon interruption of nilotinib. Eight patients completed one year of nilotinib, and were switched to Imatinib. The remaining 2 patients are currently on nilotinib as per protocol (less than 12 months since inclusion). Three patients on imatinib had to be switched back to nilotinib, because of imatinib intolerance (n=2; elevated liver transaminases and myositis) or because of loss of MMR (n=1). Therefore, at last follow up (median 64 months), 5 patients are on imatinib, 5 on nilotinib and 1 on dasatinib. All patients (100%) achieved complete hematological response (CHR) and CCyR at 3 and 18 months respectively, and maintained them thereafter. At 12 months, 6 out of 8 eligible patients achieved complete molecular response (CMR; n=3) or major molecular response (MMR; n=3). At 36 months, all eligible patients (n=7) were either in CMR (n=2) or in MMR (n=5). All patients who reached 4 years (n=6), 5 years (n=5) or 6 years (n=3) of follow up remained in either MMR or CMR. No patient developed long-term serious adverse event including cardiovascular or metabolic complications.
Conclusion: These findings suggest that imatinib can maintain MMR achieved on short-term nilotinib therapy. This strategy is a potentially safe and effective long-term treatment approach, minimizing costs and cardiovascular and metabolic complications. This however, needs confirmation with a larger number of patients.
No relevant conflicts of interest to declare.
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