Health-Related Quality of Life Impairment in Patients with Chronic Myeloid Leukemia: Results of a German Cross-Sectional Study of Patients Registered in Prospective, Controlled Clinical Trials
Authors: Saussele Susanne , Stein Mareike , Gil Arthur , Kossak-Roth Ute , Lauseker Michael , Proetel Ulrike , Einsele Hermann , Schafhausen Philippe , Lange Elisabeth , Hänel Mathias , Spiekermann Karsten , Sökler Martin , Wendtner Clemens , Kremers Stephan , Pfreundschuh Michael , Holler Ernst , Hofmann Wolf-Karsten , Hochhaus Andreas , Müller Martin C. , Hehlmann Ruediger , Pfirrmann Markus 
Published: October 2019

Abstract

Introduction: With many treatment options for chronic myeloid leukemia (CML), endpoints like health-related quality of life (HRQoL) move into focus and might be essential for deciding on treatment strategies. We sought to evaluate HRQoL in CML patients who had been registered in four consecutive studies of the German CML study group.
Methods: The EORTC QLQ-C30 questionnaire was used to assess HRQoL of CML patients. Functional scales and global health status were calculated in accordance with Aaronson (1993) and Fayers (2001). With scales ranging from 0 to 100, 8 points are regarded as a minimally important difference (Efficace et al., 2013). Baseline data of responders (R) and non-responders (NR) were compared. Associations between two variables were assessed by the Fisher or Mann-Whitney tests, as appropriate. The global health status and the functioning scores were compared between groups with the van Elteren test, if the groups were stratified for another variable. Furthermore, results of the global health status and the functioning scores in our sample were standardized in accordance with the age (18-29, 30-39, 40-49, 50-59, 60-69, ≥70 years) and sex distribution of the 2448 participants of the German HRQoL outcome study reported by Hinz et al. 2014. The outcome of our sample was then compared with the outcome of these 2448 patients representing QoL of the German population in general. Comparison was performed using a t test.
Results: A questionnaire was sent to 1634 patients. During January to April 2011, 858 questionnaires (53%) were sent back. Compared to NR, R were older (median age: 55 vs. 58, p=0.0426); years since diagnosis (median 6.5 vs. 7.4) and the percentage that had been transplanted were lower (24%vs.18%). No differences were observed regarding sex, Euro score, or time after allogeneic hematopoietic stem cell transplantation (HSCT). When answering the questionnaire, 517 (60%) patients received imatinib 400mg (IM400) and 102 (12%) were off therapy after HSCT. Less than 10% of patients received imatinib 800mg, imatinib+AraC or interferon alpha, nilotinib, or dasatinib. Time since diagnosis was ≤3 years in 156 (18%), >3 and ≤7 years in 309 (36%), and >7 years in 393 (46%) of the patients.
Women (352, 41%) perceived a significant reduction in global health status (mean: 62.7, p<0.001), role (65.4, p=0.0016), emotional (60.3, p=0.0002), and physical functioning (74.9, p<0.0001) when compared to males (68.9, 71.5, 67.6, and 82.7, respectively). In the latter two cases, this perception met the definition of a clinical relevance. Results on significance did not change with adjustment for age.
Compared to the German population, the 858 CML patients had significantly lower scores for global health status (mean: 67.9, p<0.0001), role (70.8, p<0.0001), social (69.2, p<0.0001), emotional (64.6, p<0.0001), physical (81.0, p<0.0001) and cognitive functioning (77.3, p<0.0001). Only for global health status, the difference was below 8.
To evaluate HRQoL in patients with long standing disease, 100 patients with diagnosis >7 years off therapy after HSCT and 203 patients receiving IM400 were analyzed.
Adjusted for age group and sex, CML patients receiving IM400 for more than 7 years had lower scores for global health status (mean: 63.8, p<0.0001 ), role (66.7, p<0.0001), social (68.8, p<0.0001), emotional (64.0, p<0.0001), physical (75.2, p<0.0001) and cognitive functioning (68.0, p<0.0001) than the German control population.
With respect to all six HRQoL scores, significantly lower scores than from the German population were also observed for the CML patients being seven years without treatment after HSCT: global health status (mean: 69.2, p<0.0001 ), role (68.6, p<0.0001), social (67.5, p<0.0001), emotional (68.1, p<0.0001), physical (83.1, p<0.0001) and cognitive functioning (71.2, p=0.0053).
Conclusions: In this cross-sectional study, women showed an impaired global health status, role, emotional, and physical functioning compared to males. Considering all 858 CML patients, the HRQoL was significantly impaired in all scales when compared to the German population. The same results were observed for the subgroups of patients either receiving IM400 for at least 7 years or being off therapy 7 years after HSCT.
Reduced HRQoL remains an issue for all patients after long-term TKI treatment or after HSCT. These data may serve as a basis to evaluate HRQoL in stopping studies in CML.

Disclosures
Saussele: BMS: Honoraria, Other: Travel grant, Research Funding; Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant. Kremers:Novartis: Honoraria; Bristol Myers Squibb: Other: Travel costs, supporting educational meeting; Novartis: Other: supporting educational meeting. Hochhaus:Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding. Müller:BMS: Honoraria, Other: Consulting or Advisory Role, Research Funding; Novartis: Honoraria, Other: CONSULTING OR ADVISORY ROLE, Research Funding; ARIAD Pharmaceuticals Inc.: Honoraria, Other: Consulting & Advisory Role, Research Funding. Hehlmann:Novartis Pharma: Research Funding; BMS: Consultancy. Pfirrmann:BMS: Consultancy, Honoraria; Novartis Pharma: Consultancy, Honoraria.