Souza CA, Pagnano KB, Bendit I, Conchon M, Freitas CM, Coelho AM, Funke VA, Bernardo WM Is imatinib better than second-generation tyrosine kinase inhibitors as first-line treatment of chronic phase CML? A comparison between dasatinib (100 mg) and imatinib (400 mg) as first-line treatment in chronic phase CML patients demonstrates that complete hematologic response is 11% higher, cytogenetic response is 11% higher and molecular response is 18% higher with dasatinib (NNT: 9)(41)(B). The two-year follow- up of these patients upholds the higher beneficial effect of dasatinib compared to imatinib(42)(B). Initial treatment of chronic phase CML patients using nilotinib (300 mg or 400 mg twice daily) compared to imatinib (400 mg once daily) increases the molecular response at 12 months by 22% (NNT: 5), increases the cytogenetic response by 15% (NNT: 7) and reduces the likelihood of progression to the accelerated and blast crisis phases(43)(A). In the two-year follow up, the effect of nilotinib increases the molecular response to 27% (NNT: 4), the cytogenetic response is 10% higher than imatinib (NNT: 10) with this difference being 5% lower than the evaluation at 12 months. The reduction in progression to the accelerated and blast crisis phases is maintained(44)(A). Recommendation: Dasatinib and nilotinib provide greater benefits than imatinib in the first-line treatment of chronic phase CML patients in respect to the molecular, cytogenetic and hematologic responses as well as to the progression of the disease. Does the time between diagnosis and start of treatment with imatinib have prognostic importance? In chronic phase CML patients, imatinib treatment may be started after diagnosis (early), or may be started after 24 months of treatment with interferon (late), leading to different results regarding toxicity and effectiveness. Early treatment reduces the risk of grade I and II adverse effects by 52% (NNT: 2) and grade III and IV adverse effects by 81% (NNT: 1), although it increases the risk of neutropenia and thrombocytopenia by 5% (NNH: 20). After one year of follow-up in patients who have not achieved complete cytogenetic response, early treatment produces a reduction in the risk of grade I adverse events by 3% (NNT: 33), grade II by 8% (NNT: 12) and grades III and IV by 7% (NNT: 14)(45)(B). In early treatment, there is a 16% increase in complete cytogenetic response (NNT: 7), a 2% reduction in the risk of relapse (NNT: 50) and a 15% increase in disease-free survival (NNT: 7)(45)(B). There is reduction in the risk of non-hematological adverse events with early treatment, including weight gain (11%), periorbital edema (12%), rash (9%), diarrhea (11%), and infections (19%), but there is increased risk of hemorrhage (5%) and bone pain (8%)(45)(B). Imatinib treatment at diagnosis of chronic phase CML (early treatment) increases the likelihood of major molecular response by 20% (NNT: 5) and increases the likelihood of 370 response maintenance at 30 months by 36% (NNT: 3) compared to beginning treatment one year after diagnosis (late treatment). After one year of imatinib treatment, the likelihood of loss of or not achieving molecular response is 58% lower than patients treated early (NNT: 2)(46)(B). Treatment with 400 mg imatinib produced higher major and complete cytogenetic response rates compared to the interferon and cytarabine combination in chronic phase CML patients (87.1% vs. 34.7%) and higher progression-free survival to the accelerated and blast crisis phases (96.7% vs. 91.5%; p-value < 0.001)(32)(A). Recommendation: Imatinib treatment of chronic phase CML patients should be started as early as possible after diagnosis. Does the cytogenetic evaluation have an impact on prognosis? The identification of CML patients on imatinib treatment with cytogenetic clonal evolution provides some information on the prognosis that depends on the disease phase. The presence of this change in the chronic and accelerated phases is not associated to a different cytogenetic response, however it reduces the survival rate of patients. Cytogenetic response after three months of treatment is an independent prognostic factor. The absence of complete or partial response is associated with lower survival rates(47)(B). In CML patients on imatinib treatment, the presence of a cytogenetic response increases 4-year survival by 23% (NNT: 4) and disease-free survival by 38% (NNT: 3)(48)(B). The rate of cytogenetic response in patients in late chronic phase CML after interferon alpha intolerance or resistance was 55%. After 6 years of treatment with imatinib, 77% of the patients were still with stable complete cytogenetic response, with a survival rate of 91%. Among the 124 patients who never achieved a complete cytogenetic response, 54 (44%) progressed to the accelerated or blast crisis phases(49)(B). The expected loss of cytogenetic response in the first year of imatinib treatment is 0.6%, with the mortality rate at 2 years of patients who achieved response being lower. The estimated 8-year mortality rate of these patients is 4.8%(50)(B). For CML patients unresponsive to imatinib and thus treated with second-generation TKIs (dasatinib and nilotinib), a cytogenetic response confers 20% greater survival (NNT: 5), and when associated with hematological response, the increase in the survival rate is 42% (NNT: 2)(51)(B). The presence of minor or major cytogenetic response in chronic phase CML patients under treatment with second- generation TKIs, increases event-free survival, overall survival and disease-free survival by about 25% (NNT: 4)(52)(B). Recommendation: the cytogenetic evaluation of patients under TKI treatment can predict the prognosis by complete or partial response, associated or not to other factors. Rev Bras Hematol Hemoter. 2012;34(5):367-82