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挽救性伊匹单抗治疗肉瘤样肾细胞癌具有显著疗效。

Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma.

机构信息

Department of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

出版信息

J Immunother Cancer. 2020 Feb;8(1). doi: 10.1136/jitc-2020-000584.

Abstract

BACKGROUND

Metastatic sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of RCC with generally poor prognosis. Treatment with vascular endothelial growth factor inhibitors or chemotherapy generates only short-lived responses. Recent research has suggested a role for combination checkpoint inhibition as first line treatment for metastatic sRCC. This therapy consists of induction with cytotoxic T-lymphocyte-associated protein 4 inhibitor, ipilimumab, administered with programmed cell death protein 1 (PD-1) inhibitor, nivolumab. After completion of four cycles of combination therapy, single-agent maintenance nivolumab is recommended until progression. Patients who progress on maintenance nivolumab are switched to alternate therapy. Herein, we present a case of a patient with RCC who progressed on maintenance nivolumab who, on retreatment with ipilimumab, demonstrated a significant response In addition, we summarize important findings to support the role of salvage ipilimumab in patients with sRCC.

CASE PRESENTATION

A 46-year-old man presented with flank pain and hematuria, the work up of which noted a left kidney mass for which he underwent nephrectomy and was diagnosed with localized sRCC with 60% sarcomatoid differentiation. Within 3 months of nephrectomy, he presented with recurrent flank pain and was diagnosed with recurrence of disease. He was treated with ipilimumab 1 mg/kg and nivolumab 3 mg/kg for four doses and demonstrated a partial response. He was then transitioned to single agent nivolumab maintenance. After 3 months on maintenance therapy, he was noted to have progression of disease. Given prior response to immune check point combination, it was decided to rechallenge the patient with 1 mg/kg ipilimumab. After two doses of ipilimumab and nivolumab combination therapy, the patient was noted to have a partial response. He maintained a response for an additional 9 months and treatment was eventually discontinued due to grade 3 toxicity and progression.

CONCLUSIONS

This case report demonstrates the utility of retreatment with ipilimumab as a salvage option for patients progressing on maintenance PD-1 inhibitors in metastatic RCC. Further studies are needed to identify predictors of response and toxicity to this approach, as well as the optimal scheduling of ipilimumab with maintenance nivolumab.

摘要

背景

转移性肉瘤样肾细胞癌(sRCC)是肾细胞癌的一种侵袭性变体,通常预后较差。血管内皮生长因子抑制剂或化疗的治疗仅产生短暂的反应。最近的研究表明,联合检查点抑制作为转移性 sRCC 的一线治疗具有一定作用。这种疗法包括用细胞毒性 T 淋巴细胞相关蛋白 4 抑制剂依匹单抗诱导,并用程序性细胞死亡蛋白 1(PD-1)抑制剂纳武单抗进行治疗。在完成四周期联合治疗后,建议在进展前使用单药纳武单抗维持治疗。在维持纳武单抗治疗中进展的患者将转为替代治疗。在此,我们报告了一例接受维持纳武单抗治疗后进展的 RCC 患者,在重新接受依匹单抗治疗后,显示出显著的反应。此外,我们总结了支持在 sRCC 患者中挽救性依匹单抗作用的重要发现。

病例介绍

一名 46 岁男性因腰痛和血尿就诊,检查发现左肾肿块,行肾切除术并诊断为局限性 sRCC,其中肉瘤样分化占 60%。肾切除术后 3 个月,他出现复发性腰痛,并被诊断为疾病复发。他接受了依匹单抗 1mg/kg 和纳武单抗 3mg/kg 治疗 4 个剂量,并显示出部分缓解。然后他转换为单药纳武单抗维持治疗。在维持治疗 3 个月后,他的疾病进展。鉴于之前对免疫检查点联合治疗的反应,决定重新给患者使用 1mg/kg 的依匹单抗。依匹单抗和纳武单抗联合治疗 2 个剂量后,患者的部分缓解。他又维持了 9 个月的缓解,由于 3 级毒性和进展,最终停止了治疗。

结论

本病例报告表明,对于在转移性肾细胞癌中接受 PD-1 抑制剂维持治疗后进展的患者,重新使用依匹单抗作为挽救治疗是有效的。需要进一步的研究来确定这种方法的反应和毒性的预测因素,以及依匹单抗与维持纳武单抗的最佳调度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70cb/7057424/c40d289acc03/jitc-2020-000584f01.jpg

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