晚期透明细胞肾细胞癌患者接受贝莫苏拜单抗联合安罗替尼治疗获得长期生存 1 例

Long-term survival achieved with benmelstobart plus anlotinib in a patient with advanced clear cell renal cell carcinoma：A case report

摘要

透明细胞肾细胞癌（clear cell renal cell carcinoma，ccRCC）是肾细胞癌最常见的病理类型，国际转移性肾癌数据库联盟（International Metastatic Renal Cell Carcinoma Database Consortium，IMDC）中高危患者，尤其伴多器官转移者预后较差。本文报道 1 例 IMDC 高危晚期 ccRCC 患者，男性， 65 岁，行右肾癌根治术后短期内出现肺、肝及骨多发转移，伴贫血、中性粒细胞及血小板升高，IMDC 评分5分。患者接受贝莫苏拜单抗联合安罗替尼一线治疗，治疗 6 周后影像学评估即达到部分缓解（partial response，PR），后续多次复查持续维持 PR，肿瘤总体缩小约 48% ，临床症状明显改善。治疗过程中患者出现进行性蛋白尿，经安罗替尼逐步减量后仍反复出现，最终停用靶向治疗后蛋白尿明显缓解。停用安罗替尼后患者继续接受贝莫苏拜单抗单药维持治疗，疾病持续维持深度缓解。治疗约3年后患者出现血肌酐升高，最高达 228μ mol/L ，综合考虑肾损伤及疾病稳定状态后停用免疫治疗。此后未再接受抗肿瘤治疗，直至2024年9月疾病进展并死亡，总生存期达44个月。本病例提示，在 IMDC 高危晚期 ccRCC 患者中，贝莫苏拜单抗联合安罗替尼可实现快速且持久的抗肿瘤效应，对联合治疗敏感的患者，在发生不可耐受不良反应时停用酪氨酸激酶抑制剂（tyrosine kinase inhibitors，TKIs），并转为免疫单药维持治疗，仍可能获得长期疾病控制，其机制可能与抗血管生成治疗诱导的肿瘤免疫微环境重塑及免疫记忆效应有关。本病例同时提示，在靶向联合免疫治疗过程中应重视肾毒性监测，并进行个体化治疗调整。

Abstract

Clear cell renal cell carcinoma（ccRCC）is the most common histological subtype of renal cell carcinoma.Patients classified as intermediate-or poor-risk according to the International Metastatic Renal Cell Carcinoma Database Consortium（IMDC），particularly those with multiple organ metastases ， generally have an unfavorable prognosis.Here，we report a case of advanced ccRCC in an IMDC poor- risk patient who achieved an unexpectedly prolonged survival with combination therapy followed by main- tenance immunotherapy.A 65-year-old male developed multiple metastases involving the lungs，liver， and bone shortly after undergoing radical nephrectomy for right-sided renal cancer.Laboratory findings revealed anemia，neutrophilia，and thrombocytosis，and the IMDC score was 5，indicating poor-risk disease.The patient received first-line treatment with the programmed death-ligand 1 （PD-L1）inhibitor benmelstobart in combination with the multi-target tyrosine kinase inhibitors（TKIs）anlotinib.After 6 weeks of therapy，radiological evaluation demonstrated a partial response（PR），with an overall tumor re- duction of approximately 48％.Subsequent imaging assessments confirmed a durable PR，accompanied by significant improvement in clinical symptoms and performance status.During treatment，the patient developed progressive proteinuria，with a maximum 24-hour urinary protein level of 5.18 g.Despite step- wise dose reduction of anlotinib，proteinuria recurred，necessitating discontinuation of the TKIs. Following cessation of anlotinib，the patient continued benmelstobart monotherapy as maintenance therapy and maintained sustained deep remission.After approximately 3 years of treatment，serum creatinine levels gradually increased，reaching a peak of 228μ mol/L.Considering the possibility of treatment- related renal toxicity and the durable disease control achieved，immunotherapy was subsequently discon- tinued.No further antitumor treatment was administered.The patient eventually experienced disease pro- gression and died in September 2024，with an overall survival of 44 months.This case suggests that the combination of benmelstobart and anlotinib can induce rapid and durable antitumor responses in patients with IMDC poor-risk advanced ccRCC.Notably，in patients who respond well to combination therapy， discontinuation of TKIs due to intolerable adverse events followed by maintenance immunotherapy may still provide long-term disease control.This sustained benefit may be associated with tumor microenviron- ment remodeling and the establishment of immunological memory induced by anti-angiogenic therapy. Furthermore，this case highlights the importance of vigilant monitoring of renal toxicity and individualized treatment adjustment during combined targeted therapy and immunotherapy.

关键词

肾透明细胞癌 / 免疫治疗 / 靶向治疗

Key words

Clear cell renal cell carcinoma / Immunotherapy / Targeted therapy

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基金资助

CAPTRA-STAR 科研基金项目(KY202502055)