The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study

Abstract

Abstract Background Chronic myeloid leukemia is associated with a BCR/ABL oncoprotein inhibited by imatinib mesylate, the first tyrosine kinase inhibitor. Although experimental studies have clearly demonstrated the efficacy of imatinib, up-to-date data on its effectiveness at the population level are limited. Our study aims to assess the change in disease-specific survival for chronic myeloid leukemia after introducing tyrosine kinase inhibitors in first-line treatment. Methods This study analyzed data from two population-based cancer registries in Italy. Disease-specific survival for chronic myeloid leukemia cases diagnosed before and after the introduction of tyrosine kinase inhibitors (February 2002) were calculated up to 10 years. Hazard ratios were calculated using Cox regression models adjusted for sex, age at diagnosis and residency. An interrupted time series analysis was also performed. Results Between 1996 and 2012, 357 new cases of chronic myeloid leukemia were diagnosed (standardized incidence rate of 1.2 per 100,000 residents), quite constant throughout the period. The interrupted time series analysis showed a gain of 40.4% in 5 years of disease-specific survival for chronic myeloid leukemia (from 47.3, 95%CI 38.5–55.5% to 80.8%, 95%CI 74.5–85.8%) after the introduction of tyrosine kinase inhibitors. The hazard ratio was 0.36 (95%CI 0.25–0.52) for cases diagnosed after tyrosine kinase inhibitor introduction, with differences per age at diagnosis: 74yo 0.41 (95%CI 0.23–0.73). An improvement in survival (hazard ratio 0.66, 95%CI 0.36–1.20) was also observed in cases diagnosed before, and alive at, tyrosine kinase inhibitors introduction. Conclusions Tyrosine kinase inhibitors increased disease-specific survival both for new and prevalent chronic myeloid leukemia cases. The effectiveness was similar to that observed in trials only in patients ages 65 years or younger.

Keywords

• Chronic myeloid leukemia
• Imatinib Mesylate
• Survival analysis
• Population registers
• Interrupted time series analysis