Tix Tobias, Subklewe Marion, von Bergwelt-Baildon Michael, Rejeski Kai
Department of Medicine III - Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany,
Department of Medicine III - Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Oncol Res Treat. 2025;48(4):212-219. doi: 10.1159/000542631. Epub 2024 Nov 19.
Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of hematologic malignancies, offering curative potential for patients with relapsed or refractory disease. However, the long-term survivorship of these patients is marked by unique challenges, particularly immune deficits and infectious complications, second primary malignancies (SPMs), and non-relapse mortality (NRM). Understanding and addressing these risks is paramount to improving patient outcomes and quality of life.
This review explores the incidence and risk factors for NRM and long-term complications following CAR T-cell therapy. Infections are the leading cause of NRM, accounting for over 50% of cases, driven by neutropenia, hypogammaglobulinemia, and impaired cellular immunity. SPMs, including secondary myeloid and T-cell malignancies, are increasingly recognized, prompting the FDA to issue a black box warning, although their direct link to CAR T cells remains disputed. While CAR T-cell-specific toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome contribute to morbidity, they represent only a minority of NRM cases. The management of these complications is critical as CAR T-cell therapy is being evaluated for broader use, including in earlier treatment lines and for non-malignant conditions like autoimmune diseases.
CAR T-cell therapy has revolutionized cancer treatment, but survivorship is complicated by infections, SPMs, and ultimately endangered by NRM. Prophylactic strategies, close monitoring, and toxicity management strategies are key to improving long-term outcomes.
嵌合抗原受体（CAR）T细胞疗法显著推动了血液系统恶性肿瘤的治疗，为复发或难治性疾病患者带来了治愈的潜力。然而，这些患者的长期生存面临着独特的挑战，尤其是免疫缺陷和感染并发症、第二原发性恶性肿瘤（SPM）以及非复发死亡率（NRM）。了解并应对这些风险对于改善患者预后和生活质量至关重要。
本综述探讨了CAR T细胞疗法后NRM及长期并发症的发生率和风险因素。感染是NRM的主要原因，占病例的50%以上，由中性粒细胞减少、低丙种球蛋白血症和细胞免疫受损所致。SPM，包括继发性髓系和T细胞恶性肿瘤，越来越受到认可，促使美国食品药品监督管理局（FDA）发布黑框警告，尽管它们与CAR T细胞的直接联系仍存在争议。虽然细胞因子释放综合征和免疫效应细胞相关神经毒性综合征等CAR T细胞特异性毒性会导致发病，但它们仅占NRM病例的少数。随着CAR T细胞疗法被评估用于更广泛的用途，包括早期治疗线和自身免疫性疾病等非恶性疾病，这些并发症的管理至关重要。
CAR T细胞疗法彻底改变了癌症治疗，但生存受到感染、SPM的影响，最终受到NRM的威胁。预防策略、密切监测和毒性管理策略是改善长期预后的关键。
