Abstract

The European LeukemiaNet recently published recommendations for evaluating response to imatinib among pts with CML. Criteria for failure and suboptimal responses were proposed. The significance of failure is accepted and constitutes grounds for change in treatment. The prognostic implications of having a suboptimal response are less clear making treatment decisions less clear in this setting. We analyzed the outcome of 281 pts treated with imatinib as frontline therapy for CML in CP: 73 at initial dose of 400mg daily and 208 at 800mg daily. Their median age was 48 yrs (range, 15 to 84 yrs) and their median follow-up 48 months (mo) (2–79 mo). After 3 mo of therapy none of the 273 evaluable pts met definition of suboptimal response according to the European LeukemiaNet, while 3 of 273 (1%) met definition for failure. At 6 mo 10/259 (4%) evaluable had suboptimal response and 9 (3%) failure. At 12 mo 19/246 (8%) had suboptimal and 14 (6%) failure, and at 18 mo 91/224 (41%) had suboptimal and 21 (9%) had failure. The probability of having a suboptimal response at 6 and 12 mo was significantly higher for pts treated with a starting dose of 400mg than those treated at 800mg: at 6 mo [12% suboptimal at 400mg vs 1% at 800mg (p=0.002)] and at 12 mo [17% and 4%, respectively (p<0.001)]. The outcome at 24 months* by the response at specific times was as follows:

TimeResponse% CCyR% MMR% Transf% Event
CCyR=Complete cytogenetic remission, MMR=Major molecular remission, Transf=Transformation to accelerated or blast phase, Event=loss of complete hematologic response, loss of major cytogenetic response, transformation, or death 
6 mo Optimal 91 60 
 Suboptimal 30 50 
 Failure 22 67 
 .001 .001 .001 .001 
12 mo Optimal 94 63 
 Suboptimal 56 25 16 
 Failure 21 57 
 .001 .001 .001 .001 
18 mo Optimal 98 85 
 Suboptimal 93 39 
 Failure 15 19 43 
 .001 .001 .001 .001 
TimeResponse% CCyR% MMR% Transf% Event
CCyR=Complete cytogenetic remission, MMR=Major molecular remission, Transf=Transformation to accelerated or blast phase, Event=loss of complete hematologic response, loss of major cytogenetic response, transformation, or death 
6 mo Optimal 91 60 
 Suboptimal 30 50 
 Failure 22 67 
 .001 .001 .001 .001 
12 mo Optimal 94 63 
 Suboptimal 56 25 16 
 Failure 21 57 
 .001 .001 .001 .001 
18 mo Optimal 98 85 
 Suboptimal 93 39 
 Failure 15 19 43 
 .001 .001 .001 .001 

Disclosure:Research Funding: HK and JC receive research support from Novartis.

Author notes

* Status at 24 months, regardless of whether the response in question may have been achieved earlier. There was a trend for worse outcome for pts with suboptimal response at 6 mo treated at 400mg. We conclude that patients with a suboptimal response have an inferior prognosis than those with “optimal” responses. This is particularly striking for those meeting these criteria after 6 months of therapy whose outcome mirrors that of patients with criteria for failure. Further research is needed to determine the optimal management of this group of patients.