Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: Results of a phase 3, randomized, controlled trial Journal Article


Authors: Montillo, M.; Illés, A.; Robak, T.; Pristupa, A. S.; Wach, M.; Egyed, M.; Delgado, J.; Jurczak, W.; Morschhauser, F.; Schuh, A.; Eradat, H.; Shreay, S.; Barrientos, J. C.; Zelenetz, A. D.
Article Title: Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: Results of a phase 3, randomized, controlled trial
Abstract: Background: In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δinhibitor, + bendamustine/rituximab improved progression-free survival (PFS) and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study. Methods: From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis. Results: In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo. Conclusions: Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms. © 2019 The Author(s).
Keywords: adult; controlled study; treatment response; major clinical study; overall survival; placebo; drug efficacy; rituximab; outcome assessment; progression free survival; quality of life; multiple cycle treatment; randomized controlled trial; bendamustine; multicenter study; phase 3 clinical trial; health-related quality of life; leukemia relapse; double blind procedure; chronic lymphatic leukemia; visual analog scale; self evaluation; functional assessment of cancer therapy; patient-reported outcome; idelalisib; functional assessment of cancer therapy leukemia; human; article; patient-related outcomes; randomized phase 3 study; relapsed/refractory cll; european quality of life 5 dimensions questionnaire
Journal Title: Health and Quality of Life Outcomes
Volume: 17
ISSN: 1477-7525
Publisher: Biomed Central Ltd  
Date Published: 2019-01-01
Start Page: 173
Language: English
DOI: 10.1186/s12955-019-1232-8
PUBMED: 31729982
PROVIDER: scopus
PMCID: PMC6858733
DOI/URL:
Notes: Article -- Export Date: 2 December 2019 -- Source: Scopus
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  1. Andrew D Zelenetz
    606 Zelenetz