What's Missing in Chronic Myeloid Leukemia Research: The Paucity of Studies Linking Health-Related Quality of Life to Adverse Events From the Perspectives of Patients, Physicians and Family Caregivers
Authors: Pinilla-Ibarz Javier , Navaie Maryam , Smith Jessica C. , Beaubrun Anne C. , McCullough Lauren E. , Hickey Anita H. , Toseland Ronald W. 
Published: October 2019

Abstract
Abstract 4758

Introduction:
Among patients with chronic myeloid leukemia (CML), the success of clinical care has traditionally been evaluated in terms of survival, defined clinical events (e.g., transfusions, hospital days), and test results (e.g., major molecular or cytogenetic response). However, some of these measures may not adequately describe whether patients actually show improvements in health-related quality of life (HRQoL). Conceptually, increases in HRQoL are derived from two possible effects of pharmacotherapies: (a) comparative improvement of disease symptoms, and (b) reduction of therapy-related adverse events (AEs). With the advent of tyrosine kinase inhibitors (TKIs), the leading agents in CML treatment, improved morbidity and delayed mortality have been achieved with astonishing success. Moreover, through rigorously conducted research, much has been learned about the tolerability profiles to these agents with careful delineation of AEs. Recently, there has been a growing recognition by the clinical community about the need to examine the impact of TKI-related AEs on HRQoL from the patient's perspective as well as the perspectives of their health care proxies including physicians and family caregivers. As summarized in Figure 1, the triangulation of these three perspectives in cancer care has been shown to provide valuable information that informs clinical decision-making, improves adherence to prescribed treatment regimens, and optimizes care management. Thus, the purpose of this study was to evaluate the CML literature to determine the extent to which the consequences of TKI-related AEs on HRQoL has been explored from the comparative perspectives of physicians, patients and family caregivers.

Methods:
A systematic literature review of PubMed conducted by three independent reviewers identified 44 articles using combinations of the following broad key words: CML, HRQoL, imatinib, nilotinib, dasatinib, tyrosine kinase inhibitors, adverse events, side effects and toxicity. Articles that were economic focused (n=11), commentaries (n=9), systematic reviews without HRQoL as an endpoint measure (n=7), non-English publications (n=4), studies on pediatric patients or those without CML as a primary diagnosis (n=5), non-TKI specific (n=4) or multiple publications on the same patient population (n=1) were excluded from review. The remaining 3 articles employed different study designs including cross-sectional, longitudinal and randomized clinical trial approaches with HRQoL as a primary endpoint. Collectively, they involved 1,587 CML patients treated with TKIs.

Results:
The studies were limited to patients in the chronic phase of CML when HRQoL was likely to be at its highest. The average follow-up time was short, ranging between 6 to 18 months with no long-term follow-up. None of the studies provided the comparative perspective of the physician or the primary family caregiver in relation to the patient with regards to either short-term or long-term impact of AEs on HRQoL. Rather, the studies were centered solely on the patient's reported HRQoL secondary to their experience with TKI therapy but none actually linked the type, frequency or severity of AEs to the various dimensions of HRQoL. Therefore, no information was available on which AEs have the greatest effect on what dimension of HRQoL. The most commonly reported AEs that adversely impacted HRQoL included (a) non-hematologic events related to gastroenterology, dermatology, musculoskeletal system and other (e.g., edema); and (b) hematologic events such as neutropenia, thrombocytopenia, and anemia. Across the studies, the most consistently distressing AE experienced by >80% of patients was “lack of energy”. Desired life activities, such as being able to return to work as well as the ability to participate in social and family engagements, were also rated highly in relation to better HRQoL.

Conclusions:
On the whole, little to no data are available on the temporal impact of TKI-related AEs on the multiple dimensions of HRQoL. This substantial dearth of information in the CML literature is a stark contrast to other types of cancers and therapeutic agents where the myriad of factors that affect the patient's HRQoL have been investigated from the perspectives of key stakeholders in the health care paradigm, resulting in optimal clinical decision-making and improved adherence to prescribed regimens.

Disclosures:
Pinilla-Ibarz: Novartis Pharmaceuticals Corporation: Consultancy. Navaie:Novartis Pharmaceuticals Corporation: Consultancy. Smith:Novartis Pharmaceuticals Corporation: Consultancy. Beaubrun:Novartis Pharmaceuticals Corporation: Consultancy. McCullough:Novartis Pharmaceuticals Corporation: Consultancy. Hickey:Novartis Pharmaceuticals Corporation: Consultancy. Toseland:Novartis Pharmaceuticals Corporation: Consultancy.