Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase

Abstract

Objective:

Chronic myeloid leukemia (CML) treatment relies on tyrosine kinase inhibitors (TKIs), but their use can be associated with low-grade adverse events (AEs). This analysis aimed to identify the low-grade AEs which significantly impact the Health Related Quality of Life (HRQoL) of CML patients in chronic phase (CP) and to compare the incidence of such AEs among nilotinib- and imatinib-treated patients.

Research design and methods:

Data from the 48 month ENESTnd trial were used (N = 593 patients). HRQoL was assessed using generic (SF-36) and leukemia-specific (FACT-Leu) HRQoL surveys. AEs were categorized into 26 system organ classes.

Results:

In the adjusted regression model, five low-grade AE categories – gastrointestinal disorders, blood and lymphatic system disorders, general disorders and administration site conditions, musculoskeletal disorders, and psychiatric disorders – significantly impaired at least one HRQoL score. The incidence rate of these five AE categories was either significantly lower for nilotinib than imatinib or not different between the two drugs. The AE categories with lower incidence for both nilotinib 300 mg BID and 400 mg BID versus imatinib 400 mg daily were gastrointestinal, blood and lymphatic system, and musculoskeletal; nilotinib 300 mg BID had lower incidence than imatinib for general disorders.

Limitations:

Low-grade AEs were grouped and analyzed by system organ class category, so the effect of some rare individual AEs on HRQoL may have been missed.

Conclusions:

The impact of low-grade AEs on HRQoL should be taken into account, along with other factors, when selecting the optimal treatment for patients newly diagnosed with CML-CP.

Keywords::

• Adverse effects
• Imatinib
• Myelogenous leukemia, chronic
• Nilotinib
• Quality of life

Transparency

Declaration of funding

This post-hoc analysis of the ENESTnd trial data was funded by Novartis Pharmaceuticals Corporation. The sponsor was involved in the design, collection, and analysis of information. The content of this manuscript, the ultimate interpretation, and the decision to submit it for publication was made by the authors independently.

Declaration of financial/other relationships

L.C. and C.K. have disclosed that they are employees of Novartis Pharmaceuticals Corporation and may own stock/stock options. A.G., M.M., R.I.-I., R.H., R.N., and E.Q.W. are employees of Analysis Group Inc., a company that has received consultancy fees from Novartis Pharmaceuticals Corporation.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. Reviewer 1 has disclosed that he has received a grant from BMS and has been a consultant to Novartis and BMS; Reviewer 2 has disclosed that he is an employee of Sanofi; Reviewer 3 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the ENESTnd Study Management Committee and Investigators for their contributions to the original design, implementation, and analysis of the ENESTnd trial.

The authors also thank Ana Bozas, an employee of Analysis Group Inc., who contributed to the preparation and editing of the manuscript.