Expert consensus definition of treatment intolerance in chronic myeloid leukemia in chronic phase

INTRODUCTION: Chronic myeloid leukemia in the chronic phase (CML-CP) has undergone therapeutic transformation with the advent of BCR::ABL1 tyrosine kinase inhibitors (TKIs), improving 10-year survival rates from 20% to ∼90%. These outcomes place increasing importance on maintaining quality of life (QoL), which can be compromised by adverse events (AEs) that may lead to decreased adherence or sub-therapeutic doses. Currently, there is no standardized definition of treatment intolerance, and treatment switches are based on individual physician practices. METHODS: A 13-member expert panel used a validated methodology (RAND/UCLA modified Delphi panel) to develop consensus on a definition of treatment intolerance in CML-CP. Panelists reviewed literature and provided 480 ratings on 96 unique patient scenarios that varied by TKI generation, line, and length of time on TKI treatment, frequency of AE interference on daily life, and TKI management strategies. Ratings were discussed at a meeting. RESULTS: After discussion, panelists agreed on 99% of scenarios. The group defined TKI treatment intolerance as patients whose AEs often interfered with daily activities, leading to TKI modifications. Panelists developed a tool to assess patient intolerance and recommendations for managing TKI therapy in the context of intolerance. DISCUSSION: Recognizing that treatment intolerance is influenced by laboratory findings, reported symptoms, and how patients experience their treatment, experts agreed on a patient-centered definition of TKI treatment intolerance in CML-CP. This definition represents a step forward in standardizing care for patients with CML-CP by presenting a balanced framework for managing TKI therapy, which will support shared decision-making.