Thanarajasingam Gita, Minasian Lori M, Baron Frederic, Cavalli Franco, De Claro R Angelo, Dueck Amylou C, El-Galaly Tarec C, Everest Neil, Geissler Jan, Gisselbrecht Christian, Gribben John, Horowitz Mary, Ivy S Percy, Jacobson Caron A, Keating Armand, Kluetz Paul G, Krauss Aviva, Kwong Yok Lam, Little Richard F, Mahon Francois-Xavier, Matasar Matthew J, Mateos María-Victoria, McCullough Kristen, Miller Robert S, Mohty Mohamad, Moreau Philippe, Morton Lindsay M, Nagai Sumimasa, Rule Simon, Sloan Jeff, Sonneveld Pieter, Thompson Carrie A, Tzogani Kyriaki, van Leeuwen Flora E, Velikova Galina, Villa Diego, Wingard John R, Wintrich Sophie, Seymour John F, Habermann Thomas M
Division of Haematology, Mayo Clinic, Rochester, MN, USA.
National Cancer Institute, National Institutes of Health, Department of Health & Human Services, Bethesda, MD, USA.
Lancet Haematol. 2018 Nov;5(11):e563-e598. doi: 10.1016/S2352-3026(18)30051-6. Epub 2018 Jun 18.
Tremendous progress in treatment and outcomes has been achieved across the whole range of haematological malignancies in the past two decades. Although cure rates for aggressive malignancies have increased, nowhere has progress been more impactful than in the management of typically incurable forms of haematological cancer. Population-based data have shown that 5-year survival for patients with chronic myelogenous and chronic lymphocytic leukaemia, indolent B-cell lymphomas, and multiple myeloma has improved markedly. This improvement is a result of substantial changes in disease management strategies in these malignancies. Several haematological malignancies are now chronic diseases that are treated with continuously administered therapies that have unique side-effects over time. In this Commission, an international panel of clinicians, clinical investigators, methodologists, regulators, and patient advocates representing a broad range of academic and clinical cancer expertise examine adverse events in haematological malignancies. The issues pertaining to assessment of adverse events examined here are relevant to a range of malignancies and have been, to date, underexplored in the context of haematology. The aim of this Commission is to improve toxicity assessment in clinical trials in haematological malignancies by critically examining the current process of adverse event assessment, highlighting the need to incorporate patient-reported outcomes, addressing issues unique to stem-cell transplantation and survivorship, appraising challenges in regulatory approval, and evaluating toxicity in real-world patients. We have identified a range of priority issues in these areas and defined potential solutions to challenges associated with adverse event assessment in the current treatment landscape of haematological malignancies.
在过去二十年中，血液系统恶性肿瘤的治疗和预后取得了巨大进展。尽管侵袭性恶性肿瘤的治愈率有所提高，但进展最显著的莫过于对典型的不可治愈型血液系统癌症的治疗。基于人群的数据显示，慢性粒细胞白血病、慢性淋巴细胞白血病、惰性B细胞淋巴瘤和多发性骨髓瘤患者的5年生存率有了显著提高。这一改善是这些恶性肿瘤疾病管理策略发生重大变化的结果。现在，几种血液系统恶性肿瘤已成为慢性病，需采用持续给药疗法进行治疗，随着时间推移，这些疗法会产生独特的副作用。在本委员会中，一个由临床医生、临床研究人员、方法学家、监管人员和患者权益倡导者组成的国际专家小组，代表了广泛的学术和临床癌症专业知识，对血液系统恶性肿瘤的不良事件进行了研究。本文所探讨的与不良事件评估相关的问题与一系列恶性肿瘤相关，且迄今为止，在血液学领域尚未得到充分研究。本委员会的目的是通过严格审查当前不良事件评估流程、强调纳入患者报告结局的必要性、解决干细胞移植和生存相关的独特问题、评估监管批准方面的挑战以及评估真实世界患者的毒性，来改善血液系统恶性肿瘤临床试验中的毒性评估。我们已经确定了这些领域中的一系列优先问题，并为血液系统恶性肿瘤当前治疗格局中与不良事件评估相关的挑战定义了潜在解决方案。
