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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

Underreported and underreviewed: Addressing the gaps in TKI tolerability literature for chronic myeloid leukemia

Dennis Dong Hwan Kim¹, Daniela Zackova², Massimo Breccia³

¹Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

|March 6, 2026

Abstract:

Tyrosine kinase inhibitors have transformed survival in chronic-phase chronic myeloid leukemia, yet long-term treatment success increasingly depends on treatment tolerability. Despite its recognized influence on adherence and quality of life, tolerability remains poorly defined and inconsistently addressed. To characterize existing review literature, a structured PubMed search identified review articles published between October 24, 2019, and October 23, 2024. Of 771 articles screened, 30 met inclusion criteria, 14 discussed tolerability in depth, and only 2 centered it as a primary theme. Definitions varied widely with no consensus across articles. Most reviews focused on toxicity or hospitalization, with limited coverage of low-grade, persistent adverse events or patient-reported outcomes. These findings highlight the absence of a unified understanding and prioritization of tolerability in the literature and underscore the need for a dedicated framework that clearly defines tolerability, distinguishes it from "lack of toxicity", and incorporates patient perspectives to better guide long-term CML care.

Insights

Tolerability is crucial for long-term success in chronic myeloid leukemia (CML) treatment but is poorly defined. This review highlights the need for a clear framework incorporating patient perspectives to improve CML care.

Area of Science:

Hematology
Oncology
Pharmacology

Background:

Tyrosine kinase inhibitors (TKIs) have improved survival in chronic-phase chronic myeloid leukemia (CML).
Long-term treatment success in CML is increasingly dependent on treatment tolerability.
Tolerability significantly impacts patient adherence and quality of life but lacks consistent definition and focus.

Purpose of the Study:

To characterize the existing review literature on treatment tolerability in chronic-phase CML.
To identify how tolerability is defined and addressed in current scientific reviews.
To highlight the need for a standardized approach to CML treatment tolerability.

Main Methods:

A structured PubMed search was conducted for review articles on CML tolerability.
Articles published between October 24, 2019, and October 23, 2024, were screened.
Inclusion criteria were applied to 771 initially identified articles, with 30 meeting the criteria for analysis.

Main Results:

Only 2 out of 30 included reviews focused primarily on tolerability.
Definitions of tolerability varied widely, indicating a lack of consensus.
Most reviews concentrated on toxicity or hospitalization, neglecting low-grade adverse events and patient-reported outcomes.

Conclusions:

The current literature lacks a unified understanding and prioritization of treatment tolerability in CML.
There is a critical need for a dedicated framework to define tolerability distinctly from toxicity.
Incorporating patient-reported outcomes and perspectives is essential for guiding long-term CML management.

Read full analysis

Keywords:

CML Patient-reported outcomes Quality of life TKI Tolerability Treatment outcomes

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