Management of chronic-phase CML in later lines: a Hong Kong consensus recommendation

Chronic myeloid leukemia (CML) usually requires long-term therapy with tyrosine kinase inhibitors (TKIs). While these agents have markedly advanced the clinical management and prognosis of CML, a subset of patients experience treatment resistance or suboptimal response, necessitating multiple lines of TKI therapy. Few treatment options exist for patients who are resistant or intolerant to first- and second-line therapies. To provide guidance for the management of patients in chronic-phase failing at least two lines of treatment, a literature review followed by consensus generation from an expert panel with a modified Delphi process was conducted. This was followed by a meeting in person and subsequent online iterations for the establishment of a list of consensus guidelines. Consensus was defined as ≥ 75% of respondents selecting either 'accept completely' or 'accept with some reservation'. Overall, 17 statements were formulated covering five topics - defining treatment failure and acceptable treatment response, in terms of efficacy and intolerance; sequencing therapy to prevent disease progression and improve quality of life; managing patients with broad resistance, specific mutations, and risk of cardiovascular events; considering timing of cytogenetic or molecular response; and mitigating risk when using novel therapies and allogeneic hematopoietic stem cell transplantation. These comprehensive, evidence-based recommendations will assist clinicians in managing their patients with CML in third and later lines of treatment.