Not Only Response but Early Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

 Jorge Cortes, January 2012

When I started my career in leukemia research, interferon alfa was standard therapy for patients with chronic myeloid leukemia (CML). Interferon could induce complete cytogenetic response

(CCyR; ie, 0% Philadelphia-chromosome metaphases) or partial cytogenetic response (PCyR; ie, 1% to 35%), and such responses were associated with improved survival. These responses, particularly CCyR, occurred only in a minority of patients and the time to response was not given much attention. With the introduction of tyrosine kinase inhibitors (TKIs), our goals became more ambitious, aiming for higher rates ofCCyR. For much ofthe early years ofthe TKI era, the common thought was that responses continued to occur with prolonged therapy and that 40% to 60% patients might still achieve CCyR at later times (even ifnot yet achieved during the first 12 months

of therapy). The thought at the time was that achieving a response was good enough, regardless of when it occurred. Indeed, some patients may achieve CCyR after 2 or 3 years on therapy, and some analyses suggest that time to response had limited impact in the long-term outcome of patients.  Options such as high-dose imatinib yielded higher rates of cytogenetic and molecular response and lower transcript levels at early time points, but in some studies, the response rates later became similar to those achieved with standard-dose imatinib. The value of these early responses was thus frequently questioned and considered a transient occurrence.

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