Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen, Germany.
Department of Hematology, The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, United States of America.
J Geriatr Oncol. 2024 Apr;15(3):101734. doi: 10.1016/j.jgo.2024.101734. Epub 2024 Mar 1.
Cellular therapies, including autologous stem cell transplant (ASCT), allogeneic hematopoietic cell transplantation (alloHCT), and chimeric antigen receptor- (CAR-) T cell therapies are essential treatment modalities for many hematological malignancies. Although their use in older adults has substantially increased within the past decades, cellular therapies represent intensive treatment approaches that exclude a large percentage of older adults due to comorbidities and frailty. Under- and overtreatment in older adults with hematologic malignancy is a challenge and many treatment decisions are influenced by chronologic age. The advent of efficient and well-tolerated newer treatment approaches for multiple myeloma has challenged the role of ASCT. In the modern era, there are no randomized clinical trials of transplant versus non-transplant strategies for patients ≥65 years. Nonetheless, ASCT is feasible for selected older patients and does not result in long-term compromise in quality of life. AlloHCT is the only curative approach for acute myeloid leukemia of intermediate and unfavourable risk but carries a significant risk for non-relapse mortality depending on comorbidities, general fitness, and transplant-specific characteristics, such as intensity of conditioning and donor choice. However, alloHCT is feasible in appropriately-selected older adults. Early referral for evaluation is strongly encouraged as this is the most obvious barrier. CAR-T cell therapies have shown unprecedented clinical efficacy and durability in relapsed and refractory diffuse large B cell lymphoma. Its use is well tolerated in older adults, although evidence comes from limited case numbers. Whether patients who are deemed unfit for ASCT qualify for CAR-T cell therapy remains elusive, but the tolerability and efficacy of CAR-T cell therapy appears promising, especially for older patients. The evidence from randomized trials is strong in favor of using a comprehensive geriatric assessment (CGA) to reduce treatment-related toxicities and guide treatment intensity in the care for solid tumors; its use for evaluation of cellular therapies is less evidence-based. However, CGA can provide useful information on patients' fitness, resilient mechanisms, and reveal potential optimization strategies for compensating for vulnerabilities. In this narrative review, we will discuss key questions on cellular therapies in older adults based on illustrative patient cases.
细胞疗法，包括自体干细胞移植（ASCT）、异基因造血细胞移植（alloHCT）和嵌合抗原受体（CAR）-T 细胞疗法，是许多血液恶性肿瘤的重要治疗方式。尽管在过去几十年中，这些疗法在老年患者中的应用大大增加，但由于合并症和虚弱，它们仍然排除了很大一部分老年患者。血液恶性肿瘤老年患者的治疗不足和过度治疗是一个挑战，许多治疗决策受到年龄的影响。对于多发性骨髓瘤，新的高效且耐受性好的治疗方法的出现，对 ASCT 的作用提出了挑战。在现代，对于年龄≥65 岁的患者，没有关于移植与非移植策略的随机临床试验。然而，ASCT 对于选择的老年患者是可行的，并且不会对生活质量造成长期影响。alloHCT 是中间和不良风险的急性髓系白血病的唯一治愈方法，但由于合并症、一般健康状况和移植特异性特征（如预处理强度和供者选择），它存在非复发死亡率的显著风险。然而，alloHCT 在适当选择的老年患者中是可行的。强烈鼓励早期转介评估，因为这是最明显的障碍。CAR-T 细胞疗法在复发和难治性弥漫性大 B 细胞淋巴瘤中显示出前所未有的临床疗效和持久性。其在老年患者中的应用耐受性良好，尽管证据来自有限的病例数量。对于被认为不适合 ASCT 的患者是否适合接受 CAR-T 细胞治疗仍不清楚，但 CAR-T 细胞治疗的耐受性和疗效似乎很有希望，特别是对老年患者。随机试验的证据强烈支持使用全面老年评估（CGA）来降低治疗相关毒性并指导实体肿瘤的治疗强度；其在细胞疗法评估中的应用证据较少。然而，CGA 可以提供有关患者健康状况、弹性机制的有用信息，并揭示潜在的优化策略来弥补脆弱性。在本叙述性综述中，我们将根据说明性病例讨论老年患者细胞疗法的关键问题。
