Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients.
多发性骨髓瘤（MM）主要是一种老年性疾病。近年来，一系列高效浆细胞疗法的涌现彻底改变了老年多发性骨髓瘤患者的治疗格局，其临床管理需综合考虑患者衰弱状态及年龄相关的竞争性死亡风险。传统上，新诊断老年患者的治疗核心为基于免疫调节剂（IMiDs）、蛋白酶体抑制剂（PIs）、抗CD38单克隆抗体（mAbs）及皮质类固醇的双联或三联方案，中位无进展生存期（PFS）介于34至62个月。然而，近期一系列大型III期临床试验对包含PIs、IMiDs、皮质类固醇和抗CD38 mAbs的四联方案进行了评估，结果显示其疗效显著，中位PFS可超过60个月；但联合使用PIs与IMiDs时，周围神经病变发生率较高（≥2级：27% vs. 10%），而加入抗CD38 mAbs则增加了感染风险（≥3级：40% vs. 29–41%）。T细胞重定向疗法的发展，包括T细胞衔接器（TCEs）和CAR-T细胞，进一步拓展了治疗选择。TCEs在复发疾病中显示出卓越活性，目前正在新诊断患者中进行探索性研究并已取得初步积极结果。然而，其阶梯递增给药方案常需住院实施带来的操作挑战、感染风险以及在老年患者中产生的经济负担仍是值得关注的问题。CAR-T作为目前多发性骨髓瘤领域最强效的商业化疗法，提供了“一次性治疗”的可能性。但其在老年患者中的应用受到细胞因子释放综合征、早期及迟发性神经毒性以及在衰弱患者中总体耐受性等问题的制约，目前仍缺乏该群体中的充分数据。在日益丰富的老年多发性骨髓瘤治疗体系中，如何对CAR-T与TCEs进行序贯使用仍有待明确。本综述将探讨上述疗法在老年多发性骨髓瘤患者中应用的安全性、疗效、成本及实施障碍。
肿瘤(癌症)患者之家