肿瘤细胞治疗研究
英文原题：The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T.
多发性骨髓瘤（MM）主要是一种老年疾病。
多发性骨髓瘤（MM）主要发生于老年人。近年来，高效浆细胞疗法不断涌现，改变了老年 MM 患者的治疗；对这些患者而言，衰弱状态和年龄相关的竞争性死亡原因会影响管理决策。传统上，老年初诊患者主要接受由免疫调节剂（IMiD）、蛋白酶体抑制剂（PI）、抗 CD38 单克隆抗体（mAb）和皮质类固醇组成的双药或三药联合，中位无进展生存期（PFS）为 34–62 个月。近期多项大型 III 期试验研究 PI、IMiD、皮质类固醇和抗 CD38 mAb 四药方案，显示中位 PFS 超过 60 个月，但 PI 与 IMiD 联用时周围神经病变增加（2 级：27% 对 10%），加入抗 CD38 mAb 时感染增加（3 级：40% 对 29%–41%）。T 细胞重定向疗法（包括 T 细胞衔接器［TCE］和 CAR-T）进一步扩展了治疗选择。TCE 在复发性疾病中活性显著，目前正以有希望的早期结果探索其用于初诊患者；但其阶梯式给药的实施复杂，常需住院，同时老年患者还面临感染风险和经济负担。CAR-T 是目前最强效的商业化 MM 疗法，可能实现“一次治疗即可”的模式，但在老年患者中的应用受限于对 CRS、早期及迟发神经毒性，以及衰弱患者总体耐受性的重大担忧。衰弱患者仍需要扎实的数据。随着治疗选择不断增加，CAR-T 与 TCE 在老年 MM 患者中的序贯顺序仍待确定。本综述探讨上述治疗在老年 MM 患者中的安全性、疗效、成本和实施障碍。
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.
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