摘要
直到最近,慢性淋巴细胞白血病(CLL)的临床试验还是主要集中于年轻健康的患者。然而,CLL多发于老年人,其中许多患者患有并发症,并且伴随着高龄排除积极治疗如FCR(氟达拉滨、环磷酰胺,使用利妥昔单抗)。因此,一些参数像性能状态、肾功能及合并症的数量和严重程度与临床判断应该被用来指导治疗强度的决策。两个大型的随机临床试验表明,没有接受治疗过的并发症患者,经过在苯丁酸氮芥治疗中加入抗CD20的单克隆抗体(obinutuzumab,利妥昔单抗,和ofatumumab),导致完全缓解率,速效生存期和总生存期提高(obinutuzumab连苯丁酸氮芥和利妥昔单抗组),整个过程在可接受的毒性范围内。因此,结合丁酸氮芥与抗CD20抗体和化学免疫治疗疗法是老年/并发CLL患者首选新的标准方法。在这个病人人群中,复发/难治性疾病的治疗非常具有挑战性,且这一亚群的数据相当有限。名为Bruton酪氨酸激酶抑制剂(ibrutinib) 和磷脂酰肌醇-3激酶抑制剂(idelalisib)的干扰B细胞受体信号转导的新型靶向小分子的显著疗效,从根本上改变了复发/难治性CLL的治疗模式;这些药物毒性的相对温和使他们成为老年/并发症患者的好选择。复发/难治性疾病的其他选择还有阿仑单抗,Ofatumumab,大剂量糖皮质激素+利妥昔单抗和苯达莫司汀+利妥昔单抗。本文综述了关于老年和并发CLL患者的诊断与治疗的最新知识。
关键词: 慢性淋巴细胞性白血病,并发症,健康相关的生活质量,ibrutinib,idelalisib,obinutuzumab,Ofatumumab,老年综合评估。
Current Cancer Drug Targets
Title:Therapeutic Approach to Patients with Chronic Lymphocytic Leukemia and Significant Comorbid Conditions
Volume: 16 Issue: 8
Author(s): Lukas Smolej
Affiliation:
关键词: 慢性淋巴细胞性白血病,并发症,健康相关的生活质量,ibrutinib,idelalisib,obinutuzumab,Ofatumumab,老年综合评估。
摘要: Clinical trials in chronic lymphocytic leukemia (CLL) have focused mainly on younger fit patients until recently. However, CLL is a disease of elderly and many patients have significant comorbid conditions which together with advanced age preclude the use of aggressive regimens like FCR (fludarabine, cyclophosphamide, rituximab). Therefore, parameters such as performance status, renal function and number/severity of comorbidities together with clinical judgment should be used to guide the decision-making process regarding intensity of treatment. Two large randomized trials recently demonstrated that addition of monoclonal anti-CD20 antibodies (obinutuzumab, rituximab, and ofatumumab) to chlorambucil in untreated comorbid patients lead to improvement in complete remission rate, progression-free survival and even overall survival (obinutuzumab-chlorambucil and rituximab-chlorambucil), with acceptable toxicity profile. Thus, chemoimmunotherapy combining chlorambucil with an anti-CD20 antibody is the new standard approach for elderly/comorbid CLL patients in the first line. Treatment of relapsed/refractory disease in this patient population is very challenging and data regarding this subpopulation are rather limited. Impressive efficacy of novel targeted small molecules interfering with B-cell receptor signaling, namely Bruton tyrosine kinase inhibitor ibrutinib and phosphatidylinositol-3 kinase delta inhibitor idelalisib, radically changed the treatment paradigms for relapsed/refractory CLL; relatively mild toxicity of these agents make them very good candidates for elderly/comorbid patients. Other options for relapsed/refractory disease include alemtuzumab, ofatumumab, high-dose glucocorticoids+rituximab and bendamustine+rituximab. This review summarizes the current knowledge on prognostication and therapy of elderly and comorbid patients with CLL.
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Cite this article as:
Lukas Smolej , Therapeutic Approach to Patients with Chronic Lymphocytic Leukemia and Significant Comorbid Conditions, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160408145850
DOI https://dx.doi.org/10.2174/1568009616666160408145850 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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