Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study

Noens, Lucien; Lierde, Marie Anne Van; Bock, R. De; Verhoef, Gregor; Zachée, Pierre; Berneman, Zwi N.; Martiat, Philippe; Mineur, Philippe; Eygen, Koen Van; MacDonald, Karen; Geest, Sabina De; Albrecht, Tara; Abraham, Ivo

doi:10.1182/blood-2008-12-196543

Cited by 545 publications

(543 citation statements)

References 37 publications

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“…In addition, a recent randomized study reported by Rousselot et al strongly suggests that adapting IM dose in order to reach therapeutic plasma concentrations has a favorable impact on the treatment response, which strengthens our recommendation to perform IM therapeutic drug monitoring in CML patients [9]. This recommendation is particularly important in patients with risk factors for low IM concentrations (obesity, malabsorption, multiple medications…) but should be expanded to all patients as inappropriately low IM concentrations can be observed in patients with no risk factor and as poor compliance to treatment (approximately 30% of patients) can be suspected on the basis of unusually low concentrations or of hectic results [10].…”

Section: Discussionmentioning

confidence: 62%

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Obbergh

Knoops

Devos

et al. 2017

Clinical Biochemistry

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This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400 mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p = 0.02, R 2 = 0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822 ng/mL vs 1099 ng/mL; Student's t-test, p = 0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p = 0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and major molecular response. In conclusion: in patients treated with imatinib at a fixed daily dose of 400 mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients.

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Section: Discussionmentioning

confidence: 62%

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Obbergh

Knoops

Devos

et al. 2017

Clinical Biochemistry

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“…A new challenge has arisen, however, stemming directly from the success of TKI therapy. Poor medication adherence has come into focus as a major impediment to successful treatment of patients with CML: New evidence has shown that inadequate adherence to imatinib and suboptimal outcomes are inextricably linked [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia

et al. 2012

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Dramatically improved survival associated with tyrosine kinase inhibitor (TKI) therapy has transformed the disease model for chronic myeloid leukemia (CML) to one of long-term management, but treatment success is challenged with poor medication adherence. Many risk factors associated with poor adherence can be ameliorated by close monitoring, dose modification, and supportive care. Controlling risk factors for poor adherence in combination with patient education that includes direct communication between the health care team and the patient are essential components for maximizing the benefits of TKI therapy. Am. J. Hematol. 87:687-691, 2012. V V C 2012 Wiley Periodicals, Inc. IntroductionThe last three decades have witnessed extraordinary advances in the treatment of chronic diseases, among which tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) is perhaps one of the most outstanding examples. Between 1975 and 1977, the 5-year relative survival rate of patients with CML was only 24% [1]. Allogeneic stem cell transplantation offered a potential cure for a small subset of patients; however, the risk of serious infection, graft-versus-host disease, relapse, and mortality presented substantial limitations [2,3]. The introduction of imatinib (Gleevec 1 , Novartis Pharmaceuticals Corporation, East Hanover, NJ) in 2001 replaced interferon-a as the standard of care for CML patients, with a result of remarkable improvement in patient survival. For example, the 8-year follow-up analysis of imatinib treatment in 553 CML patients participating in the International Randomized Study of Interferon versus STI571 demonstrated an overall survival (OS) rate of 85%; OS was 93% when only CMLrelated deaths and those before stem cell transplantation are considered [4]. With this prolonged survival and the recent approval of the more potent agents nilotinib (Tasigna 1 , Novartis Pharmaceuticals Corporation, East Hanover, NJ) and dasatinib (Sprycel 1 , Bristol-Myers Squibb Company, Princeton, NJ), which may be able to provide additional survival benefit, CML more closely resembles a chronic rather than a fatal disease. A new challenge has arisen, however, stemming directly from the success of TKI therapy. Poor medication adherence has come into focus as a major impediment to successful treatment of patients with CML: New evidence has shown that inadequate adherence to imatinib and suboptimal outcomes are inextricably linked [5][6][7].Difficulty in maintaining high medication adherence is not limited to TKI therapy or patients with CML, however. Indeed, the problem is pervasive across chronic conditions. For example, a 2003 report from the World Health Organization found the average rate of long-term adherence for diseases such as asthma, diabetes, hypertension, and tuberculosis was only about 50% in developed countries, and assumed to be even lower in developing countries where health resources are fewer and access to care is unpredictable [8]. The report identified five key areas that affect adherence, includin...

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“…A number of studies [12,28] show that the impact of TKI therapy (mostly imatinib) on CML control can vary by a factor of >4 depending on the local logistic conditions: organization of care, spaces available, availability of side support personnel (nurses, patient associations. .…”

Section: Logistics Of CML Treatmentmentioning

confidence: 99%

“…Although the drug is the same and the clinical conditions too, failure to address an apparently trivial symptom can result, over time, in a lack of compliance, with serious consequences. Therefore attention to the organization of the CML clinic, the availability of a critical mass of patients and the realization that these aspects are at lease at important as the choice of TKI are of fundamental importance for an optimal clinical outcome [8,28].…”

Section: Logistics Of CML Treatmentmentioning

confidence: 99%

Chronic myeloid leukemia: Second‐line drugs of choice

Gambacorti‐Passerini

Cordani

2015

American J Hematol

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The efficacy of second-line treatment for chronic myeloid leukemia (CML) plays an important role in allowing CML patients to enjoy a normal life expectancy. Four tyrosine kinase inhibitors (TKIs) are presently available: bosutinib, dasatinib, nilotinib, ponatinib. Each one has different safety and activity profiles, which are reviewed here. No controlled studies are available to guide treatment decision, which must be based on the characterization of leukemic cells, especially in cases of resistance to TKI, coupled with the safety profile of each TKI. Patient comorbidities also play an important role in the treatment decision, which can achieve a new durable response in over 50% of treated patients.

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Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study

Cited by 545 publications

References 37 publications

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia

Chronic myeloid leukemia: Second‐line drugs of choice

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