Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Clin Interv Aging. 2020 May 4;15:619-633. doi: 10.2147/CIA.S196087. eCollection 2020.
Multiple myeloma is a hematologic malignancy that predominantly affects older adults, with a median age at diagnosis of 70 years old. A mainstay of multiple myeloma treatment is lenalidomide, which is an immunomodulatory drug (IMiD) that changed the treatment paradigm for multiple myeloma. This is particularly true for older adults who do not undergo autologous stem cell transplantation (ASCT). Several pivotal trials summarized in this review demonstrate the efficacy and safety of lenalidomide in older adults with multiple myeloma, including significant improvements in response rates, progression-free survival and overall survival in the first-line and relapsed/refractory settings. Potential adverse effects include venous thromboembolism, cytopenias, and second malignancies and the doses tolerated in real-world older patients are often lower than those utilized in clinical trials enrolling select older patients. Given the heterogeneity of aging, several approaches to measuring frailty have been developed and validated to aid in predicting which older adults may benefit from empiric dose reduction to reduce the risk of toxicity and improve the tolerability of treatment. A number of randomized trials have explored a range of approaches utilizing lenalidomide in older adults in both the up-front and relapsed setting, ranging from attenuated maintenance strategies through quadruplet combination therapies including proteasome inhibitors and monoclonal antibodies. This wealth of literature provides a great number of options, which can make it difficult for a clinician to determine a single optimal recommendation for an individual patient. While lenalidomide is currently part of standard of care, the treatment of multiple myeloma is growing rapidly. There is a need to expand clinical trials participation to older adults with multiple myeloma. Incorporation of validated comprehensive geriatric assessments in clinical trials for multiple myeloma could provide a more accurate depiction of the older patient population and is an area for future exploration.
多发性骨髓瘤是一种血液系统恶性肿瘤，主要影响老年人，诊断中位年龄为 70 岁。多发性骨髓瘤治疗的主要方法是来那度胺，它是一种免疫调节药物（IMiD），改变了多发性骨髓瘤的治疗模式。对于不进行自体干细胞移植（ASCT）的老年人尤其如此。本综述总结了几项关键试验，证明了来那度胺在多发性骨髓瘤老年患者中的疗效和安全性，包括在一线和复发/难治性治疗环境中，反应率、无进展生存期和总生存期均有显著改善。潜在的不良反应包括静脉血栓栓塞、血细胞减少症和第二恶性肿瘤，真实世界中老年患者可耐受的剂量通常低于纳入特定老年患者的临床试验中使用的剂量。鉴于衰老的异质性，已经开发和验证了几种衡量虚弱的方法，以帮助预测哪些老年人可能受益于经验性剂量减少，以降低毒性风险并提高治疗的耐受性。许多随机试验已经探索了在一线和复发环境中使用来那度胺治疗老年患者的多种方法，从减弱维持策略到包括蛋白酶体抑制剂和单克隆抗体的四联组合疗法。大量文献提供了许多选择，这使得临床医生很难为个别患者确定单一的最佳建议。虽然来那度胺目前是标准治疗的一部分，但多发性骨髓瘤的治疗正在迅速发展。需要扩大多发性骨髓瘤老年患者的临床试验参与。在多发性骨髓瘤临床试验中纳入经过验证的全面老年评估，可以更准确地描述老年患者人群，这是未来探索的一个领域。
