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Objective To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p < 0.01). Decreased overall survival was associated with advanced-phase disease ( p < 0.01), failure to achieve major molecular response in first-line treatment ( p < 0.01) and interruption of first-line treatment due to any reason ( p = 0.023). Failure in achieving complete cytogenetic response and major molecular response and treatment interruption were associated with the progression to the third-line treatment. Conclusion The critical outcome observed in relapsed, intolerant or refractory chronic phase CML patients reflects the unmet need for this group of patients without an alternative therapy, such as new drugs or experimental therapies in clinical trials. Broader access to newer treatment possibilities is a crucial asset to improve survival among CML patients, especially those refractory or intolerant to first-line therapies.

Introduction: The advent of tyrosine kinase inhibitors has changed the natural history of chronic myelogenous leukemia (CML), promoting molecular remission in a high number of patients. In 40-60% of the patients that reach deep molecular responses (RM4.5 or more) and are using imatinib mesylate for 24 months or longer, a molecular response can be maintained after the cessation of the drug. Besides improving life quality in those patients, to withdraw the medication could have a great economic impact in the health system, what is extremely important in third world countries. Objective: To estimate the economic impact of stopping imatinib mesylate in CML chronic phase patients, receiving treatment for at least 36 months and presenting deep molecular response, determinate by BCR-ABL transcripts with quantitative reverse transcriptase polymerase chain reaction (QRT-PCR), in the last 24 months. Patients and methods: A single center observational retrospective study, including all patients diagnosed with chronic phase CML, confirmed by cytogenetic or molecular exams receiving treatment at a tertiary hospital in Brazil. All patients received imatinib mesylate either in first or second line therapy. Patients presenting deep molecular response for at least 24 months, under imatinib mesylate for 36 months or more were considered eligible for discontinuation the drug. The annual coast with the treatment was estimated considering the coasts of the medication and the QRT-PCR molecular exams in the Brazilian public health system. Results: In this study, 169 patients date were analyzed, the median follow up time is 5 years (range 1-13 years), 26 (15%) of those patients are eligible for stopping imatinib mesylate according to the criteria previously mentioned. Considering the requirement of QRT-PCR exams every month in the first year of discotinuating the drug, these patients would coast proximally 1.550,00 dollars/ patients year for the public health system. This coast could be reduced to 800,00 and 520 dollars/patients year, after the second and third year of the medication withdraw, when monitoring molecular response can be done every 2 and 3 months respectively. The patients receiving imatinib mesylate, and having QTR-PCR exams every six months, in the other hand, would coast the Brazilian public health system over 31.000, 00dollars /patients year. Stopping imatinib mesylate could reduce CML chronic phase treatment coasts in up to 95%. Discussion: Discontinuating imatinib mesylate is something that must be done only in clinical trial. The economic impact projection shown in this study observed the eligibility criteria described in the literature. If stopping imatinib mesylate proves to be a safe option, studies promoting it should be done in Brazil and other third world countries, as a manner of saving resources in the health system. Furthermore, the impact in life quality free of adverse effects and the possibility of gestation in young woman is not to be ignored. Disclosures No relevant conflicts of interest to declare.

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