The achievement of Complete Cytogenetic Response (CCyR, Ph+ cells 0%) with Imatinib (IM) treatment still remains a crucial objective in Chronic Myelogenous Leukemia (CML) patients. According to The European Leukemia NET guidelines, CCyR should be achieved within the 12th month of treatment. To address the incidence and prognostic role of a very early achievement of CCyR, we revised 150 chronic phase CML patients [M/F 75/75, median age 56.6 years, interquartile range (IR) 41.8 – 68.4] treated with front-line IM at our Institution from June 2002 to December 2010 who had evaluable karyotype after 3 months of treatment. At onset, median WBC and PLT counts were 75.9 × 109/l (IR 35.3 – 125.5) and 402 × 109/l (IR 281 – 592), respectively. Sokal risk score was low in 72 patients (48.2%), intermediate in 68 (44.8%) and high in 10 (7.0%); a short pre-treatment phase (< 3 months) with Hydroxyurea (HU) was administered to 132/150 patients (88.0%). Starting daily dose of IM was 400 mg in 133 patients (88.6%), 800 mg in 12 (8.0%) and 300 mg in 5 (3.4%). After 3 months of IM treatment, 118 patients (78.6%) achieved CCyR while 32 patients (21.4%) still presented Ph+ metaphases (< 33% 14 patients and ≥ 33% 18 patients) at cytogenetic analysis. At univariate analysis, factors with a negative prognostic impact on achievement of CCyR at 3 months were palpable spleen enlargement (p<0.001) and WBC count > 100.0 × 109/l at onset (p<0.001); on the contrary, sex, age > 65 years, Sokal risk score, PLT count > 500 × 109/l at onset and pre-treatment with HU did not appear to affect early CCyR achievement. Among the 118 patients in CCyR after 3 months, there were 12 failures (10.1%) during subsequent follow-up (2 suboptimal responses for molecular resistance, 7 cytogenetic relapses, 2 molecular relapses and 1 evolution to blastic phase); among the 32 patients who did not achieve early CCyR, there were 18 failures (56.2%) during subsequent follow-up (12 primary cytogenetic resistances and 6 cytogenetic relapses). The difference in the incidence of failures during follow-up in the 2 groups was highly significant (p<0.001). 5-year overall survival was 96.4% in patients achieving CCyR at 3 months and 92.1% in patients not achieving CCyR at 3 months (p=0.42); 5-year event-free survival was 83.3% in patients achieving CCyR at 3 months and 35.2% in patients not achieving CCyR at 3 months (p<0.0001). In conclusion, the achievement of CCyR at 3 months is a frequent result with IM treatment and seems unrelated to traditional prognostic factors (Sokal); furthermore, in our experience it appears to have an important prognostic role, as patients not achieving it show a significantly higher rate of failures during subsequent follow-up. Thus, the achievement of CCyR at 3 months could be a very early and useful indicator of excellent response to IM beyond ELN guidelines, making possible an early and effective identification of patients in whom more potent (but also more expensive) 2nd generation TKI are not needed.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.