Tyrosine-Kinase Inhibitors, Quality of Life and Symptom Burden in Chronic Myeloid Leukemia: What Have We Learned So Far?

Tyrosine kinase inhibitors (TKIs) have revolutionized treatment of chronic myeloid leukemia (CML) patients and quality of life (QoL) data can be of crucial importance in the current CML arena to make more informed treatment decisions. To date, a number of biomedical and laboratory data have been accumulated on clinical efficacy and toxicity of various TKIs; however, there is paucity of data on the impact of TKIs on patient outcomes.

The main objective of this systematic review is thus to quantify and to summarize all studies that have included QoL, or any other type of patient-reported outcomes (PROs) in patients with CML treated with TKIs.

A systematic review was performed, following the Cochrane methodology on all studies conducted in CML that have assessed QoL or any other type of PRO (e.g., symptom burden). The search was conducted on all full length manuscripts published up to November 2012. Candidate articles were identified mainly by PubMed, the Cochrane Library, PsycINFO and PsyArticles. Criteria for selection of studies were as follow. Types of participants: Patients diagnosed with CML, regardless of patients' age and the stage of the disease. Types of intervention: All treatments with TKIs, either used alone or in combination with other drugs. Types of outcome measures examined: Any studies including PROs were considered. Studies addressing adherence to therapy were not included. Types of studies: All type of studies were considered regardless of the design (e.g., prospective or cross-sectional study). No restriction in the number of enrolled patients or type of analysis (e.g. qualitative or quantitative) was applied. Two reviewers independently evaluated all candidate abstracts retrieved from electronic databases based on the above selection criteria. Extracted data from full length manuscripts were crosschecked and discrepancies resolved by consensus. The reviewers abstracted a number of basic features of the studies, including the type of treatment, the measures used to assess QoL and clinical characteristics of patients enrolled. Also, a summary of main PROs findings was provided.

Six studies, enrolling overall 2171 CML patients, were identified up to November 2012. None of these studies were published before 2003. Out of six studies, two were conducted on a national level and four recruited patients in an international setting. Four studies reported QoL data of patients treated with imatinib, one on bosutinib and the other one included patients receiving various TKIs. QoL of patients younger than 60 years, who are in treatment with long-term imatinib therapy is greatly impaired when compared with that of their peers in the general population. This study suggests that although the less toxic profile of TKIs therapies is unquestionable, still much has to be done to further improve patient's QoL and reduce symptom burden. Also, another study suggested that fatigue is the main factor influencing QoL regardless of the type of TKIs. Some data also indicates that physicians might underestimate the importance of symptoms. Another study, conducted in patients treated with bosutinib, showed that QoL profile of patients who have failed first line Imatinib therapy, due to either resistance or intolerance, is not different. Second line therapy with bosutinb provide clinically meaningful QoL improvements in imatinib-intolerant patients (but not in imatinib-resistant patients). Remarkably, no study was identified measuring QoL, or any other type of PROs, in patients treated with dasatinib or nilotinib. Two studies reported a gender effect, showing that male tend to report better QoL outcomes than female patients.

This systematic review revealed the paucity of evidence base data in this area. However, QoL assessments in these CML studies emphasize the unique information provided by the patient's perspective on the burden of the disease and treatment. Investigators are encouraged to include PROs in future CML studies to obtain additional meaningful data to make more informed treatment decisions.

Efficace:Novartis: Research Funding; Bristol Myers Squibb: Honoraria.