PO.CL05.04 · 临床研究
肾移植受者中的免疫检查点抑制剂治疗：抗肿瘤活性与移植物排斥风险的真实世界结局
Immune checkpoint inhibitor therapy in kidney transplant recipients: Real-world outcomes of antitumor activity and graft rejection risk
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：肾移植受者（KTR）罹患侵袭性恶性肿瘤的风险显著升高，但由于对移植物排斥的担忧以及缺乏前瞻性证据，免疫检查点抑制剂（ICI）在这一人群中的使用仍然受限。我们评估了ICI治疗在患有晚期癌症的KTR中的真实世界抗肿瘤活性、移植物安全性以及免疫抑制相关结局。
方法：我们回顾性分析了2018-2025年间在单一三级中心接受治疗的57例患有局部晚期不可切除或转移性恶性肿瘤的KTR。33例接受ICI治疗，24例接受非ICI系统性治疗。结局指标包括客观缓解率（ORR）、临床获益率（CBR）、无进展生存期（PFS）、自诊断起的总生存期（OSd）、自治疗开始起的总生存期（OSt）、急性移植物排斥以及免疫相关不良事件（irAE）。肿瘤缓解按RECIST v1.1评估。
结果：与非ICI治疗相比，ICI治疗患者取得了更高的ORR（40.0%对26.1%）和CBR（60.0%对33.3%）。中位OSd为35.8对23.3个月，中位PFS为4.3对3.5个月（两者均无统计学意义）。ICI治疗的中位OSt显著更长（15.1对7.9个月；p=0.012）。ICI治疗患者中12.1%发生急性排斥（3%不可逆），而系统性治疗为4.2%；排斥事件在发生时间上具有异质性（3周至14个月），且大多对冲击剂量皮质类固醇有反应。ICI患者中27.3%发生irAE，12.1%为≥2级事件，无治疗相关死亡。在皮肤鳞状细胞癌（cSCC）亚组（n=33）中，ICI治疗产生的ORR为47.4%，CBR为63.2%，相对于对照组有生存改善的趋势。
结论：ICI在KTR中产生了具有临床意义的抗肿瘤活性，尤其在cSCC中，在精心量身定制的免疫抑制下移植物排斥率可控。尽管历史上存在较高的担忧，但不可逆的移植物丢失并不常见。这些发现支持在经过筛选的移植受者中开展ICI治疗的可行性，并凸显了免疫抑制策略在平衡抗肿瘤疗效与移植物安全性方面的重要性。需要开展前瞻性、整合生物标志物的研究，以确定这一高危人群在PD-1阻断期间的最佳免疫抑制方案。
查看英文原文 English abstract
Background: Kidney transplant recipients (KTRs) have a markedly elevated risk of aggressive malignancies, yet the use of immune checkpoint inhibitors (ICIs) in this population remains limited by concerns for allograft rejection and the absence of prospective evidence. We evaluated real-world antitumor activity, graft safety, and immunosuppression-related outcomes of ICI therapy in KTRs with advanced cancers.
Methods: We retrospectively analyzed 57 KTRs with locally advanced unresectable or metastatic malignancies treated between 2018-2025 at a single tertiary center. Thirty-three received ICIs and 24 received non-ICI systemic therapy. Outcomes included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival from diagnosis (OSd), overall survival from treatment initiation (OSt), acute allograft rejection, and immune-related adverse events (irAEs). Tumor response was assessed by RECIST v1.1.
Results: ICI-treated patients achieved higher ORR (40.0% vs 26.1%) and CBR (60.0% vs 33.3%) compared with non-ICI therapy. Median OSd was 35.8 vs 23.3 months, and median PFS was 4.3 vs 3.5 months (both not statistically significant). Median OSt was significantly longer with ICIs (15.1 vs 7.9 months; p=0.012). Acute rejection occurred in 12.1% of ICI-treated patients (3% irreversible) versus 4.2% with systemic therapy; rejection events were heterogeneous in timing (3 weeks-14 months) and largely responsive to pulse-dose corticosteroids. IrAEs occurred in 27.3% of ICI patients, with grade ≥2 events in 12.1%, and no treatment-related deaths. In the cutaneous squamous cell carcinoma (cSCC) subgroup (n=33), ICI therapy produced an ORR of 47.4% and CBR of 63.2%, with trends toward improved survival relative to controls.
Conclusions: ICIs produced clinically meaningful antitumor activity in KTRs, particularly in cSCC, with a manageable rate of allograft rejection under carefully tailored immunosuppression. Despite higher historical concerns, irreversible graft loss was uncommon. These findings support the feasibility of ICI therapy in selected transplant recipients and highlight the importance of immunosuppression strategy in balancing antitumor efficacy and graft safety. Prospective, biomarker-integrated studies are needed to define optimal immunosuppression during PD-1 blockade in this high-risk population.
利益披露 Disclosure
A. Rezazadeh Roudkoli, None..
E. Barbir, None..
S. Kavousi, None..
M. A. Aboelatta, None..
C. Haivas, None..
B. Smith, None..
A. Kukla, None.
A. Z. Dudek,
Iovance Other, Participation in Advisory Board.
TTC Oncology, LLC g., Board of Directors, non-salaried role), Stock.
IDEAYA Biosciences Other.
Immunocore Other.
Kumquat Biosciences, INC Other.
Replimune Other.
Pierre Fabre Medicament Other.