Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia

Tim H. Brümmendorf,Carlo Gambacorti-Passerini,Joseph C. Cappelleri,Carla Mamolo,Arlene Reisman,Andrew G. Bushmakin,Andrea Viqueira,Susanne Isfort

doi:10.1007/s00277-020-04018-1

Abstract

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR.

Highlights

Tyrosine kinase inhibitors (TKIs) that block the activity of the BCR-ABL1 gene fusion product, the hallmark of chronic myeloid leukemia (CML), have substantially improved efficacy and tolerability of treatment and extended patient life expectancy to nearly that of the general population [1]
Assessment of patient-reported outcome (PRO) with the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire was an exploratory objective of the BFORE trial; after 12 months of treatment with either bosutinib or imatinib, patients in the modified ITT population maintained or improved health-related quality of life (HRQoL) compared with baseline [11]
Treatment is continued for 5 years until the end of the study or until treatment failure, unacceptable toxicity, Data from the ITT population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) in both arms of the BFORE trial were used to examine relationships between molecular responses (MR) and patient-reported HRQoL

Summary

Introduction

Tyrosine kinase inhibitors (TKIs) that block the activity of the BCR-ABL1 gene fusion product, the hallmark of chronic myeloid leukemia (CML), have substantially improved efficacy and tolerability of treatment and extended patient life expectancy to nearly that of the general population [1]. Assessment of PROs with the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire was an exploratory objective of the BFORE trial; after 12 months of treatment with either bosutinib or imatinib, patients in the modified ITT population maintained or improved HRQoL compared with baseline [11]. We examined the relationships between MR and HRQoL in newly diagnosed patients with CP CML receiving TKI treatment in the BFORE trial, using a pooled analysis of the bosutinib and imatinib arms To our knowledge, this is the first detailed investigation of the association between efficacy outcomes and HRQoL in this patient population using data from a randomized phase 3 clinical trial. Patients were asked to complete FACT-Leu questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion [11]

Methods

Results

Discussion