Improved survival boosts the prevalence of chronic myeloid leukemia: predictions from a population-based study
16 Apr 2016-Journal of Cancer Research and Clinical Oncology (Springer Berlin Heidelberg)-Vol. 142, Iss: 7, pp 1441-1447
TL;DR: The number of chronic myeloid leukemia (CML) patients in Germany is expected to increase further until at least 2040–2050 with a maximum of more than 20,000 CML patients as the most probable scenario.
Abstract: Purpose
Due to prolonged survival, there will be many more chronic myeloid leukemia (CML) patients alive in the future. The aims of this work were to estimate the current prevalence of CML by using routine data and to project future patient numbers in Germany.
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TL;DR: Higher out-of-pocket expense for TKI therapy is significantly associated with worse HRQoL in persons with chronic-phase CML in CCyR receiving TKI Therapy, indicating the importance of drug cost and health insurance policies on people’s HRQeL.
Abstract: To explore health-related quality-of-life (HRQoL) profiles and identify socio-demographic and clinical variables associated with HRQoL in persons with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKIs). A cross-sectional questionnaire was distributed to adults with chronic-phase CML receiving tyrosine kinase-inhibitor (TKI) therapy >3 months in complete cytogenetic response (CCyR). Respondents were anonymous. SF-36 Health Survey was used to measure HRQoL. Data from 828 respondents were analyzable. 524 (63%) were male. Median age was 42 years (range 18–88 years). 648 (78%) were receiving imatinib. Median TKI-therapy duration was 36 months (range 3–178 months). 638 (77%) paid some or all of their TKI costs. Annual out-of-pocket expenses >$4600 USD was associated with lower physical component summary (PCS; −2.8 to −3.8; P = 0.0081 and 0.0009) and mental component summary (MCS; −2.1 to −4.3; P = 0.0394 and 0.0080) in multivariate analyses. Other variables significantly associated with a lower PCS and/or MCS included: (1) female sex; (2) increasing age; (3) education level < bachelor degree; (4) co-morbidity(ies); and (5) generic drug use. TKI-therapy duration 3–5 years was associated with higher PCS and MCS. Higher out-of-pocket expense for TKI therapy is significantly associated with worse HRQoL in persons with chronic-phase CML in CCyR receiving TKI therapy. These data indicate the importance of drug cost and health insurance policies on people’s HRQoL.
20 citations
Cites background from "Improved survival boosts the preval..."
...Persons with CML now have a similar life-expectancy to the general population and numbers of people living with CML is increasing (Gambacorti-Passerini et al. 2011; Sasaki et al. 2015; Bower et al. 2016; Huang et al. 2012; Gunnarsson et al. 2016; Lauseker et al. 2016)....
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TL;DR: Results obtained from dose optimization and discontinuation trials currently in progress will help practitioners determine the best dose and duration of dasatinib for patients with CML, because treatment decisions will be made through continued discussions between physicians and patients.
Abstract: Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed with tyrosine kinase inhibitor therapy. Now that long-term survival has been achieved in patients with CML, the focus of treatment has shifted to dose optimization, with the goal of maintaining response while improving quality of life. In this review, the authors discuss optimizing the dose of the second-generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for dasatinib in the first and later lines of treatment were established through long-term (5-year and 7-year) trials. Recently published data have indicated that further dose optimization may maintain efficacy while minimizing adverse events. Results obtained from dose optimization and discontinuation trials currently in progress will help practitioners determine the best dose and duration of dasatinib for patients with CML, because treatment decisions will be made through continued discussions between physicians and patients. Cancer 2018;124:1660-72. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
18 citations
Cites background from "Improved survival boosts the preval..."
...Thus, economic considerations beyond the personal may play a role in seeking the lowest effective dose of dasatinib or of any TKI.27 Many of these cost concerns may be mitigated in the future, as approved generic versions of TKIs become available....
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...Reductions and/or interruptions may be preferred by patients when discontinuing dasatinib is not an option; administering a lower dose of dasatinib, after initiating treatment at the approved dose, may be preferable to switching to another TKI.16 Moreover, modifying doses (lowering or interrupting) to mitigate toxicity may help to improve adherence.11 Cancer April 15, 2018 1663 In addition to minimizing AEs, economic concerns may drive the decision to lower daily doses for some patients.26 In one study, 41 patients with CML-CP were treated with a mean dose of dasatinib of 92 mg 6 23 mg per day while achieving and maintaining efficacy, although the quality of the responses was not reported.26 The driving force for reducing doses in this study appears to have been financial, rather than a reduction in AEs....
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...Thus, economic considerations beyond the personal may play a role in seeking the lowest effective dose of dasatinib or of any TKI.(27) Many of these cost concerns may be mitigated in the future, as approved generic versions of TKIs become available....
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TL;DR: Social-economic and clinical variables were significantly associated with PROs in persons with CML receiving TKI-therapy and better well-being, and adverse impact on daily life and work was significant associated with more interests in TKIs and less impact on subject’s dailylife and work.
Abstract: Explore patient-reported outcomes (PROs), including health-related quality of life (HRQoL), satisfaction with therapy, impact of the therapy on work and daily life, and concerns related to the therapy and identify variables associated with PROs in persons with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKIs). Across-sectional questionnaire was distributed to adults with chronic phase CML and answered anonymously. SF-36 Health Survey was used to measure HRQoL. Our focus was on the physical component summary (PCS) and mental component summary (MCS) components. Data from 819 respondents receiving TKI-therapy ≥3 months and achieving a complete cytogenetic response were analyzed. Median age was 42 years (range 18–88 years). 652 (80%) were receiving imatinib. Median TKI-therapy duration was 36 months (range 3–178 months). 629 (77%) paid some or all of their TKI costs. In multivariate analyses, female sex, increasing age, lower education level, increasing co-morbidities, concomitant medication, ≥3 symptoms, moderate or severe symptom, switch from imatinib to a second-generation TKI, and higher annual out-of-pocket expense of TKI were significantly associated with lower PCS and/or MCS. However, TKI-therapy duration 3–7 years was significantly associated with better well-being. Higher PCS or MCS score was significantly associated with higher satisfaction level with TKI-therapy and less impact of TKI-therapy on subject’s daily life and work. In addition, adverse impact on daily life and work was significantly associated with more interests in TKI-therapy-related issues. Social-economic and clinical variables were significantly associated with PROs in persons with CML receiving TKI-therapy.
13 citations
Cites background from "Improved survival boosts the preval..."
...Persons with CML now have a similar life expectancy to the general population and numbers of people living with CML are increasing (Gambacorti-Passerini et al. 2011; Sasaki et al. 2015; Bower et al. 2016; Huang et al. 2012; Gunnarsson et al. 2016; Lauseker et al. 2016)....
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TL;DR: It is concluded that dasatinib, similar to nilotinib, has the adverse impact on glucose-lipid metabolism compared with imatinib.
Abstract: To explore the differences in glucose-lipid metabolism profiles among the 3 TKIs, we designed a retrospective study to compare the onset of hyperglycaemia, hypertriglyceridemia, hypercholesterolemia and hyper-low density lipoprotein (LDL)-cholesterolemia in the patients with normal baseline glucose-lipid profiles and had no medical record of cardio- or cerebro-vascular diseases and/or metabolic syndrome diseases, and identify variables associated with them. 370 chronic myeloid leukaemia patients receiving dasatinib, nilotinib or imatinib therapy ≥3 months were retrospectively reviewed. During TKI-therapy, the mean fasting glucose, triglyceride, cholesterol, and LDL-cholesterol levels increased significantly in both dasatinib and nilotinib cohorts compared with the imatinib cohort. In multivariate analyses, dasatinib was the factor significantly associated with both poor hyperglycaemia- and hypertriglyceridemia-free survival. In addition, nilotinib was significantly associated with more occurrences of hyperglycaemia and hypercholesterolemia; increasing age was significantly associated with more occurrences of hyperglycaemia and hypertriglyceridemia. We concluded that dasatinib, similar to nilotinib, has the adverse impact on glucose-lipid metabolism compared with imatinib.
10 citations
01 Jan 2018
TL;DR: The authors ask for further research on the occurrence of secondary malignancies, other therapy-related risks, treatment of elderly patients, economic impact on healthcare systems by the expensive long-term treatment, and chances to stop treatment with TKIs in patients with complete remission without risking relapse of CML.
Abstract: Although some epidemiological information on Philadelphia (Ph)/BCR-ABL-positive chronic myeloid leukemia (CML) is available, etiological data are still sparse. CML incidence rates vary from 0.6 to 2.8 cases per 100,000 inhabitants with an obvious increase in age, and men are more often affected than women. Geographic and/or ethnic variations and diagnostic accurateness might contribute to the seen variability. CML can be induced by acute high-dose ionizing radiation exposure or exposure to benzene and some other chemicals. Prevalence rates have increased from 3.9 (1985) to 11.9 (2012) per 100,000 inhabitants mainly due to the widespread use of tyrosine kinase inhibitors (TKIs). Recently, an 8-year overall survival (OS) of 89% was published. This outstanding therapeutic achievement asks for further research on the occurrence of secondary malignancies, other therapy-related risks, treatment of elderly patients, economic impact on healthcare systems by the expensive long-term treatment, and chances to stop treatment with TKIs in patients with complete remission without risking relapse of CML.
5 citations
References
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TL;DR: Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors.
Abstract: Summary Background Imatinib treatment significantly improves survival in patients with chronic myeloid leukaemia (CML), but little is known about whether treatment can safely be discontinued in the long term. We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib. Methods In our prospective, multicentre, non-randomised Stop Imatinib (STIM) study, imatinib treatment (of >2 years duration) was discontinued in patients with CML who were aged 18 years and older and in CMR (>5-log reduction in BCR–ABL and ABL levels and undetectable transcripts on quantitative RT-PCR). Patients who had undergone immunomodulatory treatment (apart from interferon α), treatment for other malignancies, or allogeneic haemopoietic stem-cell transplantation were not included. Patients were enrolled at 19 participating institutions in France. In this interim analysis, rate of relapse was assessed by use of RT-PCR for patients with at least 12 months of follow-up. Imatinib was reintroduced in patients who had molecular relapse. This study is registered with ClinicalTrials.gov, number NCT00478985. Findings 100 patients were enrolled between July 9, 2007, and Dec 17, 2009. Median follow-up was 17 months (range 1–30), and 69 patients had at least 12 months follow-up (median 24 months, range 13–30). 42 (61%) of these 69 patients relapsed (40 before 6 months, one patient at month 7, and one at month 19). At 12 months, the probability of persistent CMR for these 69 patients was 41% (95% CI 29–52). All patients who relapsed responded to reintroduction of imatinib: 16 of the 42 patients who relapsed showed decreases in their BCR–ABL levels, and 26 achieved CMR that was sustained after imatinib rechallenge. Interpretation Imatinib can be safely discontinued in patients with a CMR of at least 2 years duration. Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors. Funding French Ministry of Health (Programme Hospitalier de Recherche 2006 grants), Institut National du Cancer (INCA).
1,363 citations
TL;DR: Survival in CML has significantly improved since 2001, particularly so in CP-AML and AP-CML, and Imatinib therapy minimized the impact of known prognostic factors and Sokal risk in CP -CML and accentuated theimpact of age in AP- and BP-C ML.
295 citations
TL;DR: The objective of this report was to estimate the increasing prevalence and plateau prevalence of CML in future years.
Abstract: BACKGROUND:
The annual incidence of chronic myeloid leukemia (CML) in the United States is approximately 4800 cases. With the success of tyrosine kinase inhibitor (TKI) therapy, the all-cause annual mortality rate was reduced to 2%. Therefore, the prevalence of CML is increasing over time. Estimating the CML prevalence and plateau prevalence is important in the implementation of health care strategies and future therapeutic trials. The objective of this report was to estimate the increasing prevalence and plateau prevalence of CML in future years.
METHODS:
The prevalence of CML was estimated based on several parameters: the annual mortality rate on TKI therapy compared with a age-matched, normal population; the incidence of CML; the anticipated population growth in the United States; and aging of the population.
RESULTS:
On the basis of these calculations, the mortality ratio of patients with CML compared with an age-matched normal population was approximately 1.53. The estimated prevalence of CML is approximately 70,000 in 2010, 112,000 in 2020, 144,000 in 2030, 167,000 in 2040, and 181,000 in 2050, when it will reach a near plateau prevalence.
CONCLUSIONS:
The current results indicated that the prevalence of CML will continue to increase to reach a near plateau prevalence 35 times the annual incidence. These estimates should be considered in health care policies and in the design of future studies in CML. Cancer 2012;118: 3123–27. © 2012 American Cancer Society.
238 citations
"Improved survival boosts the preval..." refers background in this paper
...Huang et al. (2012) recently published an estimation of the future prevalence of CML in the USA....
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TL;DR: This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM.
Abstract: Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% Cls) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) fo...
202 citations
Ludwig Maximilian University of Munich1, University of Bologna2, Masaryk University3, Palacký University, Olomouc4, Tartu University Hospital5, Helsinki University Central Hospital6, French Institute of Health and Medical Research7, University of Catania8, Vilnius University9, VU University Medical Center10, Gdańsk Medical University11, University of Belgrade12, Uppsala University13, Royal Liverpool University Hospital14, Novartis15, Heidelberg University16
TL;DR: The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection, and from a clinical point of view the results of most trials can be generalized to most countries.
Abstract: This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
166 citations