Addressing unmet needs in chronic myeloid leukemia in chronic phase treated with two or more tyrosine kinase inhibitors: insights from literature and Indian clinical practice

INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder, usually diagnosed in its chronic phase (CP), often requiring life-long therapy. Despite the effectiveness of targeted therapy with tyrosine kinase inhibitors (TKIs), resistance or intolerance may occur, requiring a switch. The probability of achieving guideline-recommended cytogenetic and molecular responses declines from first (1 L) to second (2 L) and subsequent lines. About half of the patients receiving third line TKI treatment exhibit resistance or intolerance to prior TKIs. Post-2 L, patients experience non-durable responses, persistent adverse events, and a decreased quality of life. AREAS COVERED: This narrative review is based on targeted literature search in Medline via PubMed and expert clinical input from Indian hematologists to cover unmet needs of patients with CP-CML post-2 L of TKI therapy. We present an overview of the available clinical data, outline the challenges associated with treatment resistance and intolerance, identify gaps in patient management, and discuss personalized treatment approaches that could bridge these gaps and improve patient outcomes post-2 L. EXPERT OPINION: Management of CP-CML beyond 2 L remains a significant clinical challenge due to resistance, intolerance, and suboptimal long-term responses with currently available TKIs. Integrating newer agents like asciminib or ponatinib, can help overcome resistance and improve patient outcomes.