How to Initiate Treatment for Chronic Myelogenous Leukemia

Jerald P. Radich, MD, Director of the Molecular Oncology Lab at the Fred Hutchinson Cancer Research Center, and Professor of Medicine at the University of Washington School of Medicine

Q: What is your basic approach to handling a middle aged adult patient in good general health who is referred to you with a new diagnosis of Chronic Myelogenous Leukemia?
A: First off, the treatment of choice for chronic phase CML is a tyrosine kinase inhibitor (TKI). Currently there are three approved TKIs in the front line setting, imatinib and the second generation TKIs, nilotinib and dasatinib. There have been three randomized trials comparing imatinib to either nilotinib or dasatinib, and all three show remarkably similar results. The second generation TKIs have better short term efficacy (cytogenetic and molecular responses at 12 months), and fewer progressions to advanced phase disease, yet surprisingly, overall survival seem similar between imatinib and the newer agents. This is especially relevant since imatinib may soon become generic.
All of the TKIs are well tolerated, and each have specific toxicities. For example, nilotinib can cause elevations in metabolic syndrome manifestations (lipids, glucose), while dasatinib can cause pleural effusions and in rare occasions, pulmonary hypertension.
In choosing a TKI, a few things are important to consider, and they revolve around the goals of therapy, which should be different for different patients. One important consideration is risk of progression at the time of diagnosis. There are several clinical prognostic scores available (Sokal, Hasford, EUTOS) that correlated with outcome. Patients with low risk disease can safely be treated with any TKI, while if a patient has a clinical presentation at high risk, it might be better to start with a more potent second generation TKI. Secondly, it is now becoming clear that some patients who achieve an outstanding disease response can discontinue therapy and not relapse. Thus, for a younger patient who might be facing decades of TKI therapy, or who may wish to have children, a second generation may be a good starting point, since the chance to achieve a complete molecular response is greater than with imatinib. However for the lion’s share of patients, starting with imatinib is a fine choice, particularly in older patients, or those with higher risk of cardiovascular complications, since imatinib seems relatively free of these complications compared to the more potent TKIs.
Lastly, if generic imatinib becomes far cheaper than other TKIs, there are some solid medical economic arguments that might compel one to start therapy with imatinib.
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