Department of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
J Immunother Cancer. 2020 Feb;8(1). doi: 10.1136/jitc-2020-000584.
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.
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.
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.
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。
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。
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。