The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors

Abstract

The development of the oral tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) is one of the great triumphs of cancer research. Although the efficacy of TKIs has dramatically improved the disease-specific overall survival rate, the prevalence of CML is increasing worldwide. Currently, CML patients receive prolonged (even lifelong) treatment, and over the last decade, clinical decision making has become challenging. Therefore, consideration of the effects of TKI therapies on patients' quality of life (QoL) and symptom burden (ie, patient-reported outcomes [PROs]) is now critical to more robustly inform patient care and improve health care quality. Over the last 5 years, a number of studies have generated valuable PRO data, for example, on long-term QoL effects of imatinib therapy or symptom burden of patients switching from imatinib to second-generation TKIs. PRO findings are important, as they provide a unique patient perspective on the burden of the disease and treatments effects. We will review main evidence-based data on the use of PROs in clinical research and highlight the importance of methodological rigor of PRO assessment. Also, we will describe the potential value of using PRO assessment in routine clinical practice, for example, to facilitate timely management of side effects. Areas for future research will also be discussed.

Figure 1.

Percentage of newly diagnosed CP-CML patients who reported the listed side effects of imatinib. The data are from 5 prospective, company-sponsored, Good Clinical Practice, contract research organization–monitored studies testing imatinib vs interferon-α plus low-dose arabinosyl cytosine (IRIS) vs nilotinib (ENESTnd) vs dasatinib (DASISION and SWOG)^, and vs bosutinib (BELA). In the original reports, the figure represented the proportion or percentage of patients reporting each side effect. In all studies, the sum of the figures was >100%, because many patients reported >1 side effect. The differences among each side effect underscore the variability in collecting and reporting side effects, although all patients were treated frontline with the same dose of imatinib (400 mg/d). The differences among studies are quite impressive. The difference is also impressive for grade 3/4 side effects: from a total of 18.1% in IRIS to a total of 3.6% in ENESTnd (data not shown). Adapted from Baccarani et al. Image and legend obtained from the Haematologica Journal website (www.haematologica.org) and reproduced with permission of the rights holder (Ferrata Storti Foundation, Pavia, Italy).

Figure 2.

The importance of monitoring patient-reported QoL and symptom burden over time. *For a number of reasons (including side effects), it is possible that QoL might decline at any point along the disease/treatment trajectory. Also, it is likely that the QoL decline might not be as steady as shown in this figure (the trend of the QoL curve reported here is for descriptive purposes only). †One goal of first-line TKI therapy should be to ensure optimal QoL for as long as possible. Any effort should be made to maintain an “acceptable” QoL level for each patient (ie, before reaching the critical threshold below which the risk of poor adherence behavior is heightened).