Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia

Abstract

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...

A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR-ABL+ leukemias

“…25 Variable compliance with long-term therapy, with approximately one-third of patients stopping TKIs altogether, and the development of mutations that provide resistance to TKIs, frequently results in treatment failure, which sometimes leads to accelerated phase or blast crisis. 26,27 Long-term use of TKIs used to suppress leukemia leads to a myriad of side effects, including pleural edema, effusions, pulmonary hypertension, sepsis, gastrointestinal problems, and lethal cardiovascular events. 28,29 Furthermore, outside of stem cell transplantation (SCT), there is no effective therapy of CML in blast crisis or Philadelphia chromosome positive (Ph 1 ) ALL 30 ; treatment with TKIs results in brief responses only.…”

Adherence and/or discontinuation of imatinib mesylate in patients with chronic myeloid leukemia

“…Each assessment tool has advantages and disadvantages that favor or limit their applicability (Pérez-Escamilla et al, 2015). A systematic review of over 6500 citations, with full review of 549 articles published between 1967 and 2001, showed there is no effective approach to assess adherence and that most of the methods used to evaluate adherence in a context of chronic diseases are generally complicated, expensive, and not consistently successful (Jabbour et al, 2012a). Thus, the authors suggest the combination of methods to monitor medication adherence with the purpose of reducing biases and inherent limitations to each instrument.…”

“…In this situation, many patients respond to tyrosine kinase inhibitors of second generation such as dasatinib and nilotinib, which are more potent drugs than imatinib and can improve the quality of life of patients with this clinical condition (Jabbour et al, 2012a;Bhamidipati et al, 2013). However, the survival rate of patients with CML adherent to imatinib is 16.9% higher compared to nonadherent patients.…”

“…It can be performed by direct methods such as detection of drug or metabolite in biological fluids, addition of a biological marker and direct observation of the patient and/or indirect methods, which are simple and easy to perform such as patient diary, questionnaires, drug records, frequency of medication withdrawal in pharmacies, electronic monitoring of medication and manual pill count (Jabbour et al, 2012a;Pérez-Escamilla et al, 2015).…”

Cultural factors related to adherence to imatinib in CML: A Mexican perspective

“…1 From a progressive disease with a poor prognosis, CLM evolved into an illness that permits an adequate quality of life and an overall survival rate greater than 80% at 5 years. 2 Imatinib presents the possibility of a simple, safe, oral, and highly effective outpatient treatment, but at considerable cost.…”