Evaluations of the ‘real-world’ efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide, population-based, chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagnosed between January 2008 and April 2013 in the Netherlands. The registry covered 457 patients; 434 in chronic phase (95%) and 15 (3%) in advanced disease phase. Seventy-five percent of the patients in chronic phase were treated with imatinib and 25% with a second-generation tyrosine kinase inhibitor. At 3 years 44% of patients had discontinued their first-line treatment, mainly due to intolerance (21%) or treatment failure (19%). At 18 months 73% of patients had achieved a complete cytogenetic response and 63% a major molecular response. Deep molecular responses (MR4.0 and MR4.5) were achieved in 69% and 56% of patients, respectively, at 48 months. All response milestones were achieved faster in patients treated upfront with a second-generation tyrosine kinase inhibitor, but ultimately patients initially treated with imatinib also reached similar levels of responses. The 6-year cumulative incidence of eligibility for a tyrosine kinase cessation attempt, according to EURO-SKI criteria, was 31%. Our findings show that in a ‘real-world’ setting the long-term outcome of patients treated with tyrosine kinase inhibitors is excellent and the conditions for an attempt to stop tyrosine kinase inhibitor therapy are met by a third of the patients.

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Patients with chronic myeloid leukemia (CML) in deep molecular remission may discontinue tyrosine kinase inhibitor (TKI) treatment without relapse. The present study aims to gain insight into the views of CML patients on TKI treatment discontinuation and identify factors that are associated with their willingness to discontinue treatment. A cross-sectional study, among adult Dutch CML patients was conducted to assess willingness and their views on benefits of and concerns about discontinuation. A total of 185 patients participated of whom 76% were willing to discontinue TKI-treatment. Patients considered the absence of side effects the most important benefit whereas fear of disease recurrence was their most prominent concern. Adequate monitoring was the most important prerequisite for TKI-treatment discontinuation. However, ambiguity with respect to perquisites indicate that patients on long-term TKI treatment should be adequately informed both on the possibility to discontinue treatment and on its benefits, risks, and measures that address risks.

Introduction Chronic myeloid leukemia (CML) is a relatively rare condition with approximately 170 new patients per year in the Netherlands. Patients at risk of progression to advanced stage disease need to be identified based on their molecular BCR-ABL1response, for which detailed guidelines are available. We evaluated the quality of molecular monitoring in Dutch clinical practice. Methods Chronic phase CML patients with a minimum of one year available follow-up were abstracted from a real-world population based registry of patients newly diagnosed between January 2008 and April 2013 in the Netherlands (PHAROS-CML). Hospitals were categorized into three groups based on the average number of CML-treatment initiations per year: low (<1/year), intermediate (1-2/year) and high volume (>2/year). The minimum standard of care was defined as molecular monitoring of response at least three times in the first year of treatment. Results In 253 eligible patients, molecular response assessment within the first year after diagnosis was performed a minimum of three times in 78%, twice in 15%, once in 4% and not performed in 3% of patients. Treatment for these patients was initiated in 54 different hospitals, corresponding to an average just below 1 new CML patient per year per hospital. In univariate logistic regression analysis treatment in an academic hospital, clinical trial inclusion, hospital volume and first line second generation TKI (2GTKI) treatment proved to be significant predictors of the minimum standard of care. Only the latter two remained significant predictors in multivariate analysis. Treatment was initiated for 153 patients (61%) in high volume hospitals (n=16), 66 patients (26%) in intermediate volume hospitals (n=18) and 34 patients (13%) in low volume hospitals (n=20). In the high volume hospitals, 90% of patients received the minimum standard of care, compared to 67% in the intermediate (p<.001) and 50% in the low volume hospitals (p<.001). Moreover, monitoring in imatinib treated patients was poorer than in patients initially treated with 2GTKI (74% vs 94%, p=.002). Conclusion Approximately 40% of newly diagnosed CML patients in the Netherlands are treated within centres that see less than two new patients per year. Such low treatment volumes are associated with a substandard quality of molecular response monitoring. Surprisingly, patients treated with imatinib as first line treatment are monitored less stringent, even though the rate of treatment failure is known to be higher than 2GTKI treated patients. Our observations support a potential patient benefit of centralization of CML treatment. Disclosures Janssen: Novartis: Research Funding; ARIAD: Consultancy; BMS: Honoraria; Pfizer: Honoraria.