Clinical Scenario: Disease and Patient-Related Factors Affecting Treatment Selection in the Frontline Setting

In this clinical case, a 68-year-old asymptomatic woman with a history of heavy smoking, hypertension, obesity, and reflux presented with lab abnormalities found during a routine checkup. She was noted to have hyperleukocytosis with a left shift and splenomegaly. Her calculated Sokal Index score was 1.38, placing her in the high-risk category. Risk stratification tools such as the Sokal Index remain a routine part of evaluation, particularly in academic settings, as they guide initial treatment decisions and long-term management strategy.

Given the patient’s high-risk disease features and comorbidities, treatment selection requires careful consideration. Although all approved TKIs remain options, higher-risk patients often benefit more from second-generation TKIs or newer agents that offer greater potency and faster molecular responses. In this case, the goal of treatment-free remission should remain a long-term target, and initiating therapy with a potent agent may better position the patient for deep, sustained molecular response, which is a prerequisite for that goal.

However, comorbid conditions such as obesity, prior smoking history, and gastrointestinal issues influence the choice of specific agents. Some TKIs are associated with higher risks of vascular or pulmonary adverse events, which could complicate treatment in patients with predisposing factors. For this patient, selecting a TKI with a favorable safety profile in the context of her risk factors is key. Although no option is absolutely contraindicated, newer agents with improved tolerability and fewer cardiovascular or pulmonary risks may be more suitable. Ultimately, treatment choice should be individualized, weighing efficacy, adverse effect profiles, and patient-specific factors to optimize both outcomes and quality of life.