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.

The Multiple sclerosis functional composite (MSFC) has been recommended as a clinical outcome measure to be used in future MS trials. A specific characteristic of the MSFC is that it is defined as a measure of impairment relative to a reference population. Using different reference populations affects actual MSFC scores. If the selection of a reference population also has an effect on sensitivity to change of the MSFC, comparison of data from clinical trials will be almost impossible when different reference populations are used We studied the effect of the selection of a reference population on the outcome of a trial by simulating 343 intervention trials and comparing results obtained by using three different reference populations: two previously published MS patient populations and a healthy population. Scores of the healthy population were collected in the first part of the study. The effects of sex, age and education level on test scores of healthy subjects were studied as well. In the healthy controls, sex, age and education level had a different impact on individual test scores of MSFC components and overall MSFC score. Our study shows that, with the use of the MSFC, the selection of different reference populations does not affect the trial statistics and significance, but it does affect comparability of results between different trials, and complicates the dinical interpretation of any observed change.

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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.

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