Health-Related Quality of Life In Patients with Chronic Myeloid Leukemia: What Have We Learned Over the Last Twenty Years?.
Authors: Efficace Fabio , Breccia Massimo , Baccarani Michele , Vignetti Marco , Mandelli Franco 
Published: October 2019

Abstract
Abstract 3423

Background:
Ensuring the highest possible standards of health-related quality of life (HRQOL) in patients with CML is now one of the top priorities of clinical research. There are several examples of how HRQOL data have contributed in better understanding overall treatment effectiveness in patients diagnosed with cancer malignancies. However, no evidence exists regarding the amount and the quality HRQOL research conducted in CML patients.

Aim:
The main objective of this paper is to systematically review all evidence-base data available, published over the last twenty years, stemming from studies focusing on HRQOL and other patient-reported outcomes (PROs) in CML patients.

Materials and Methods:
A systematic review broadly following the Cochrane methodology was performed. A literature search was undertaken in a number of databases by two independent reviewers. The following databases were used: PubMed (1980- October 2009), Cumulative index of Nursing and Allied Health Literature (CINHAL), SCOPUS (1980-2009), PsycINFO and PsycARTICLES (1980-2009). Additional literature was identified via the reference lists of these articles and a search of references was also performed by hand. Key experts in the field of hematological research were contacted. Candidate articles were then also independently scrutinized for possible inclusion. Any original article including a HRQOL evaluation or any other type of PROs (according to the current definition by the Food and Drug Administration) was considered. Any study regardless of the treatment, design and type of analysis (quantitative or qualitative) was considered eligible. No restrictions in the number of patients enrolled was applied. All studies meeting the criteria were then independently evaluated by two reviewers on their methodological quality according to a previously developed protocol. This included a number of methodological and statistical quality criteria such as questionnaire used, timing of assessment, missing data documentation, and discussion of HRQOL outcomes in terms of clinical significance.

Results:
Over 350 articles were scrutinized for possible inclusion in the review and 15 met inclusion criteria. No studies were published before 1995 and 10 studies (67%) were published after year 2000. Six studies (40%) dealt with interferon (IFN) based-treatments, 7 (47%) with bone marrow transplantation (BMT) and 2 (13%) with targeted therapies. Only 5 (33%) studies included an overall sample of more than 100 CML patients thus providing more confidence on HRQOL analysis. The EORTC QLQ-C30 was the most frequently used HRQOL measure being employed in 4 (27%) studies. Evidence stemming from studies comparing IFN with conventional hydroxyurea or busulfan treatments highlighted major HRQOL impairment associated with IFN even in the long run. These were particularly evident in a number of functional areas: cognitive, social, and sexual functioning as well as for symptoms: fatigue, pain and dyspnea, nausea/vomiting, flu-like and febrile, skin problems. Neuropsychological limitations and mood disorders were also found to be associated with IFN based-therapy. As concern BMT, current evidence suggests that even in the long run (i.e. 10 years after transplantation) physical limitations are still evident when compared to age matched general population norms. Although two studies dealing with targeted therapies were found to have included a HRQOL component in the study design, only one fully documented HRQOL outcomes. This was a randomized controlled trial (IRIS Study) (HRQOL being used a secondary endpoint) showing a clear advantage in terms of HRQOL of Imatinib over IFN based therapy. The difference between treatment arms (IM vs. IFN) was not only statistically significant but also clinically meaningful and with a large effect size (ES=1.05).

Conclusions:
HRQOL evidence base data is scarce in CML patients. The main conclusion that can be drawn is that IM offer major advantages in terms of HRQOL compared with IFN based therapies. However, long-term HRQOL data of IM therapy are needed to determine the impact of therapy over the long run from the patients' perspective. We expect patient-reported HRQOL becoming more and more a crucial outcome to fully evaluate overall treatment effectiveness of future therapeutic approaches in this area.

Disclosures:
No relevant conflicts of interest to declare.