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Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.

Background and Objective: Interferon-a (IFN) is increasingly being used as the drug of choice in chronic myeloid leukemia patients. The main objectives of the study were to study the influence of the classic prognostic variables and response to IFN, and to assess the influence of this response on the course of the disease and survival., Design and Methods: Single arm, prospective, multicenter study, without a control group. Only Ph1-positive CML patients were included. The treatment scheme was biphasic: the patients first received standard chemotherapy and thereafter IFN-a2a was used as monotherapy, with a target dose of 9 MU/d/s.c., Results: Twenty-one centers in Spain enrolled 132 patients (72 men, 60 women). The median dose of IFN given was 5.8 MU/d, and the median treatment duration was 431 days (range: 18-2,597). Seventy-two percent of patients obtained a hematologic response in the first six months of IFN treatment. Genetic response was obtained in 47% of the patients, and the response was major or complete in 27% and 19%, respectively. The median time to obtain this response was 7, 9, and 18 months for minimal, partial and complete genetic response, respectively. Multivariant analysis showed that only a higher percentage of basophils at diagnosis was associated with a worse hematologic response at six months (p=0.001) (OR: 1.23) and with a worse cytogenetic response in the first year of IFN therapy (p=0.018) (OR: 1.4). Over an observation period of 8 years, 35.6% of the patients died, and 85 (64.4%) remained alive. With a median follow-up of 42 months (3.7-98), the 6-year projected probabilities of survival and transformation-free survival were 0.61+/-0.07 vs. 0.54+/-0.07, respectively. Patients with Kantarjian's stage 3 disease or in a high-risk Sokal group had lower probabilities of survival, but these systems did not adequately discriminate in our series. Obtaining a complete hematologic response in the first six months of IFN therapy was favorable in terms of overall survival (p=0.05; HR=0.33). Cox's analysis demonstrated that obtaining a cytogenetic response in the first year was independently associated with better overall survival (p=0.04; HR=0.19) and better transformation-free survival (p=0.0035; HR=0.11)., Interpretation and Conclusions: Nearly half of the patients obtained some degree of Philadelphia suppression, which was major in 27%, and complete in 19%. A higher percentage of basophils at diagnosis was the only variable associated with a lower probability of cytogenetic response. Obtaining a cytogenetic response during the first year of IFN treatment was a favorable and independent variable in terms of survival and transformation-free survival. Obtaining a major cytogenetic response during this period decreased the risk of transformation twenty times. Our results suggest that the effect of IFN on survival is independent of the classic prognostic variables.