Abstract
BackgroundChronic 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.MethodsThis 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.ResultsBetween 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: <65yo 0.17 (95%CI 0.08–0.39), >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.ConclusionsTyrosine 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.
Highlights
Chronic myeloid leukemia is associated with a BCR/ABL oncoprotein inhibited by imatinib mesylate, the first tyrosine kinase inhibitor
From 1996 to 2012, 357 new cases of chronic myeloid leukemia were diagnosed in the provinces of Modena and Reggio Emilia
The trend in incidence rates was substantially constant (APC -2.3, 95%CI -5.1-0.6) (Fig. 1) while the mean age at diagnosis was higher for cases diagnosed before drug introduction (63.4 years, 95%CI 60.3– 66.5) compared to those diagnosed after February 1, 2002 (59.5 years, 95%CI 57.0–61.9)(coef = − 3.9, p = 0.048)
Summary
Chronic myeloid leukemia is associated with a BCR/ABL oncoprotein inhibited by imatinib mesylate, the first tyrosine kinase inhibitor. Our study aims to assess the change in disease-specific survival for chronic myeloid leukemia after introducing tyrosine kinase inhibitors in first-line treatment. Chronic myeloid leukemia (CML) is a myeloproliferative clonal disorder resulting from a neoplastic transformation of hematopoietic stem cells [1]. The diagnosis of CML requires the detection of the BCR/ABL oncoprotein [6]. In cases diagnosed before introducing the detection of BCR/ABL as diagnostic criterion, the protein was present in 95% of CML patients [7]. The BCR/ABL oncoprotein is selectively inhibited by imatinib mesylate [8], the first tyrosine kinase inhibitor (TKI). Imatinib mesylate has transformed CML from a fatal to a chronic disease. Thanks to the results of IRIS (International Randomized Study of Interferon and STI571, [9]), imatinib was granted marketing authorization within the European Union by EMA (European Medicines Agency) in November 2001 [10] and in the USA by the Food and Drug Administration in May 2001
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