Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.

OBJECTIVES: The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. METHODS: In a population-based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. RESULTS: The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular "warning." The development of additional cytogenetic abnormalities was always accompanied with molecular failure. CONCLUSION: We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re-assessment should still be performed when molecular response is suboptimal.

Treatment outcome in a population-based, 'real-world' cohort of patients with chronic myeloid leukemia.

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.