Complete Cytogenetic Response After 3 Months Is a Very Early Indicator of Good Response to Imatinib As Front-Line Treatment in Chronic Myelogenous Leukemia,

Abstract 3783

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 12^th 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) 2^nd generation TKI are not needed.