Campagnaro Erica L, Goebel Teresa E, Lazarus Hillard M
University of Michigan, 1500 E. Medical Center Drive, SPC 5911, Ann Arbor, MI, 48109-5911, USA,
Drugs Aging. 2015 Jun;32(6):427-42. doi: 10.1007/s40266-015-0265-x.
Plasma cell myeloma (PCM) is a hematologic malignancy that primarily affects the elderly. Approximately two-thirds of patients are aged 65 years or older at diagnosis. Major advances in testing, treatment, and supportive care have resulted in substantial improvement in overall survival in younger, standard-risk, PCM patients over the past 3 decades. However, this positive impact progressively diminishes with advancing age, with some studies showing no improvement in survival outcomes in the elderly. Slow improvement in survival for elderly PCM patients is likely multifactorial, influenced by factors such as age-related physiologic changes, increased comorbidities, decreased treatment tolerance, socioeconomic barriers, and possible differences in disease biology. The standard approach of basing treatment decisions on age and performance status does not account for this complexity, and can be insufficient to determine the risks and benefits of treatment. Comprehensive geriatric assessment (CGA) produces a more thorough iteration of the factors influencing an individual's treatment risk, and can potentially identify targets for intervention to lower risk. Ongoing studies are looking at developing and refining the tools available for risk screening and assessment. Treating elderly PCM patients with novel agent-based regimens with or without autologous stem cell transplantation has improved response rates and survival in some studies, but elderly PCM patients have benefitted less than their younger counterparts from recent advances in PCM treatment. Personalizing treatment decisions, based on predictions of risk, determined by geriatric assessment, and response, determined by precision medicine (our understanding of the genetic, molecular, and cellular pathways that drive an individual's cancer) will help maximize the benefit and minimize the risk of PCM treatment for each patient. Continued evaluation of new strategies and treatments for PCM in clinical trials specifically designed for elderly patients is needed to continue to improve outcomes for elderly PCM patients in the future.
浆细胞骨髓瘤(PCM)是一种主要影响老年人的血液系统恶性肿瘤。约三分之二的患者在确诊时年龄在65岁及以上。在过去30年中,检测、治疗和支持性护理方面的重大进展使年轻的、标准风险的PCM患者的总生存率有了显著提高。然而,随着年龄的增长,这种积极影响逐渐减弱,一些研究表明老年患者的生存结果没有改善。老年PCM患者生存率的缓慢改善可能是多因素的,受年龄相关的生理变化、合并症增加、治疗耐受性降低、社会经济障碍以及疾病生物学可能存在的差异等因素影响。基于年龄和体能状态做出治疗决策的标准方法无法考虑到这种复杂性,可能不足以确定治疗的风险和益处。综合老年评估(CGA)能更全面地考量影响个体治疗风险的因素,并有可能识别出降低风险的干预靶点。正在进行的研究着眼于开发和完善用于风险筛查和评估的工具。在一些研究中,采用含新型药物方案联合或不联合自体干细胞移植治疗老年PCM患者提高了缓解率和生存率,但与年轻患者相比,老年PCM患者从PCM治疗的最新进展中获益较少。根据老年评估确定的风险预测以及精准医学(我们对驱动个体癌症的基因、分子和细胞途径的理解)确定的反应来个性化治疗决策,将有助于使每位PCM患者的治疗获益最大化并将风险最小化。未来需要在专门为老年患者设计的临床试验中持续评估PCM的新策略和治疗方法,以继续改善老年PCM患者的治疗结果。