CML Treatment in Dutch Hospitals with Low Patient Volumes Is Associated with a Substandard Quality of Molecular Response Monitoring

Abstract

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.

Differences in treatment and monitoring of chronic myeloid leukemia with regard to age, but not sex: Results from a population‐based study

“…This might be a reason why the observed number of cytogenetic analyses is lower than recommended. These results are in accordance with the work of Geelen et al 15 Some years ago, we had reported differences in survival between teaching hospitals, municipal hospitals, and office-based physicians. 35 Here we found differences with regard to cytogenetic but not with regard to molecular evaluations.…”

“…A regular cytogenetic and/or molecular monitoring has been considered necessary for a successful treatment and a prolonged survival. [13][14][15] However, it has been shown that at least in the United States, the number of molecular examinations is far away from the guidelines' recommendations. 16 Thus, the aim of our study was to evaluate whether the prescribing of TKIs and the subsequent monitoring of patients with CML in Germany follow the current European LeukemiaNet (ELN) recommendations and whether prescribing is sufficient to allow for a satisfactory patients' compliance.…”

The potential health gain and cost savings of improving adherence in chronic myeloid leukemia

“…Preliminary results from a national populationbased study showed inadequate monitoring in the first year of TKI treatment in 28% of the newly diagnosed CML-CP patients in the Netherlands, whereas patients who received optimal molecular monitoring had a significant higher overall survival [9]. This is consistent with other studies, showing that 54% of the patients were monitored less than 3 times a year and had a significantly higher risk of progression to advanced phase disease and death [10].…”

“…When these response criteria are not met and patient adherence is optimal, the TKI received as current treatment should be substituted with an alternative TKI. In the Netherlands, a rate of patients receiving adequate molecular monitoring of 72% was observed [9].…”

“…The current physician adherence to guidelines regarding adequate molecular monitoring in the Netherlands is 72% [9]. The current situation yields 13.95 QALY and mean costs of e452,578 per patient over a period of 25 years.…”