Frontline CP-CML Treatment Selection: Treatment-related Toxicities and the Minimally Effective Dose

Some treatment-related toxicities can be particularly challenging for patients with CP-CML, especially those receiving tyrosine kinase inhibitors (TKIs). Among the most difficult to tolerate are fatigue, arthralgia/myalgia, gastrointestinal symptoms (e.g., nausea or diarrhea), and cardiovascular events, particularly with second-generation TKIs. These side effects can significantly impact quality of life and adherence, especially when persistent or severe. In some cases, patients may discontinue treatment due to intolerance rather than lack of efficacy.

Certain adverse events, such as fatigue, joint or muscle aches, and low-grade gastrointestinal symptoms, may improve over time with continued therapy. However, this varies by individual and drug. Some patients adapt physiologically or psychologically to these side effects, especially if the benefits of treatment are clear and support is provided early on. In contrast, more serious toxicities—like pleural effusion or metabolic disturbances—may worsen or remain problematic and often require intervention or a change in therapy.

There are several strategies that can help mitigate common side effects and improve tolerability. These include dose adjustments, switching to a different TKI, symptomatic management (e.g., NSAIDs for musculoskeletal pain, antiemetics for nausea), and supportive care measures such as physical activity and nutritional guidance. In some cases, using a TKI with a better safety profile—such as asciminib—may be appropriate, especially for patients with comorbidities or prior intolerance. Early identification and proactive management of side effects are essential to maintain adherence and optimize outcomes.