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

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. 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. 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. 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.

慢性期慢性髓系白血病（chronic myeloid leukemia in the chronic phase, CML-CP）的治疗模式随着BCR::ABL1酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）的问世发生了根本性转变，患者10年生存率从20%提升至约90%。这一治疗突破使得维持患者生活质量（quality of life, QoL）的重要性日益凸显，而不良事件（adverse events, AEs）可能导致患者治疗依从性下降或给药剂量不足，进而损害其生活质量。当前临床尚未形成统一的治疗不耐受定义，治疗方案的切换仍依赖医师的个体临床实践。由13名专家组成的咨询团队采用经过验证的兰德-加州大学洛杉矶分校改良德尔菲法（RAND/UCLA modified Delphi panel），就CML-CP的治疗不耐受定义达成共识。专家团队回顾了相关文献，并针对96种涵盖TKIs代次、治疗线数、用药时长、不良事件对日常生活的干扰频率以及TKIs管理策略等变量的独特患者场景，完成了480份评分。随后专家召开会议对评分结果进行充分讨论，最终在99%的场景中达成一致意见。该团队将TKIs治疗不耐受定义为：不良事件频繁干扰患者日常活动，进而需要调整TKIs治疗方案的情况。专家团队还开发了用于评估患者治疗不耐受的工具，以及针对不耐受场景下TKIs治疗管理的推荐方案。鉴于治疗不耐受受实验室检查结果、患者自述症状以及患者自身的治疗体验共同影响，专家们最终达成了以患者为中心的CML-CP患者TKIs治疗不耐受定义。这一定义提出了平衡的TKIs治疗管理框架，有助于推动CML-CP患者诊疗的标准化进程，将为医患共同决策提供有力支撑。