Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.

中文翻译：

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评估耐受性的纵向毒性随时间 (ToxT) 分析：CALGB 50401（联盟）试验中来那度胺的案例研究。


耐受性评估对于长期接受治疗的血液恶性肿瘤患者越来越重要。这些药物的不良事件可能会影响患者长期耐受治疗的能力。常规毒性表包括由不良事件通用术语标准定义的高级不良事件的发生率，不提供有关这些不良事件的时间概况的信息，也不反映与以下情况特别相关的持续的、较低级别的症状毒性：惰性疾病患者的治疗耐受性。必须采用现代方法来评估和报告毒性，以了解患者对治疗的耐受性。在本观点中，我们对 CALGB 50401（联盟；NCT00238238）试验中治疗的滤泡性淋巴瘤患者中来那度胺和来那度胺联合利妥昔单抗的不良事件进行了重点、试点和纵向毒性随时间的推移分析，以确定不良事件的轨迹和量化连续的低级别事件的负担。随时间的毒性分析提供了由来那度胺引起的中性粒细胞减少症和疲劳轨迹的临床相关描述，这些描述未通过不良事件通用术语标准定义的最高级别事件的标准分析来识别。系统、严格地将患者报告的结果纳入临床试验对于我们了解血液恶性肿瘤患者长期治疗的耐受性至关重要。