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Complete response to perioperative treatment using nivolumab for metastatic renal cell carcinoma: A case report.

ABSTRACT: We report a case of 59-year-old woman who has multiple lung metastases with renal cell carcinoma (RCC). She received neoadjuvant therapy using nivolumab following sunitinib. Thereafter, we performed cytoreductive nephrectomy and subsequently administered nivolumab. We also found a high expression of PD-L1 in tumor cell and infiltration of lymphocytes with CD8 expression by immunohistochemistry. A complete response was achieved 4 months after surgery. A perioperative treatment using nivolumab might be useful treatment for metastatic RCC.

SUBMITTER: Ikarashi D

PROVIDER: S-EPMC6562266 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Complete response to perioperative treatment using nivolumab for metastatic renal cell carcinoma: A case report.

Ikarashi Daiki D Nakamura Yasuyuki Y Shimodate Hitoshi H Usui Yoshitaka Y Ujiie Takashi T Obara Wataru W

Urology case reports 20190130

We report a case of 59-year-old woman who has multiple lung metastases with renal cell carcinoma (RCC). She received neoadjuvant therapy using nivolumab following sunitinib. Thereafter, we performed cytoreductive nephrectomy and subsequently administered nivolumab. We also found a high expression of PD-L1 in tumor cell and infiltration of lymphocytes with CD8 expression by immunohistochemistry. A complete response was achieved 4 months after surgery. A perioperative treatment using nivolumab mig ...[more]

PMID: 31211050

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Project description:In an immune-competent context nivolumab showed long-term benefit in overall survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, in special cancer population such as these patients with immunodeficiency and viral infections, data on checkpoint inhibitors (ICI) activity are scant. Herein, we report a patient with a Human papilloma virus (HPV)-related oropharyngeal cancer (OPC) and CD4 lymphocytopenia. After a first-line treatment complete remission, the patient experienced Human Polyomavirus (JCV) infection in the brain. Consequently, to the recovery from progressive multifocal leukoencephalopathy (PML) the patient metastasized and was enrolled in a single-arm trial with nivolumab (EudraCT number: 2017-000562-30). A complete and durable response (more 3 years) was observed after 10 nivolumab injections Q2wks, interrupted for persistent drug related G2 diarrhea and a syndrome of inappropriate antidiuretic hormone secretion. We describe the circulating immune profile (before-, during-, and after nivolumab), consistent with the clinical history. Moreover, during nivolumab treatment, brain MRI evidenced the presence of small punctuate areas of contrast enhancement, reflecting a mild immune response in perivascular spaces. By cytofluorimetry, we observed that during JCV infection the CD4/CD8 ratio of the patient was under the normal values. After JCV infection recovery and before nivolumab treatment, CD4/CD8 ratio reached the normality threshold, even if the CD4+ T cell count remained largely under the normal values. During ICI, gene expression xCell analyses of circulating immune cells of the patient, showed a progressive normalization of the total immune profile, with significant boost in CD4+ and CD8+ T cells and a reduction in NK T, comparable to the circulating immune profile of reference tumor-free HNSCC patients. The present case supports the activity of ICI in a population of special cancer patients; whether JCV and HPV infections (alone or together) might have a possible role as immune booster(s), require further investigations.

Project description:Background: Renal cell carcinoma is the third most prevalent urological cancer worldwide and about 30% of patients present with metastatic disease at the time of diagnosis. Systemic treatments for metastatic renal cell carcinoma have improved recently. Vascular endothelial growth factor targeting therapies were the previous standard of care. However, immune checkpoint inhibitors used in second line therapy have now been shown to improve patient survival. We report a case of metastatic renal cell carcinoma with nivolumab as a second-line therapy after progression with tyrosine kinase inhibitor therapy. Unusual adverse events in metastatic renal cell carcinoma, such as vitiligo, were observed in this patient who developed a remarkable documented pathological complete response to his renal tumor. Case presentation: A 60-year-old caucasian male was diagnosed with a pulmonary metastatic clear cell renal cell carcinoma. Sunitinib was used as first line treatment without success. He received nivolumab in second-line treatment. He developed several immune-related adverse events, most notably vitiligo. The patient had a radiological complete response on metastatic sites, with a significant decrease of renal tumor volume and underwent cytoreductive nephrectomy after 2 years of treatment, confirming the pathological complete response. The patient remains disease-free for 10 months without further systemic therapy after nivolumab discontinuation. Conclusions: Pathological complete response with nivolumab in metastatic renal cell carcinoma is rare. This case further highlights the potentially predictive role of immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma and raises questions concerning the role of nephrectomy after immune checkpoint inhibitor therapy. Further studies are needed to better identify predictive factors for treatment response to immunotherapy in metastatic renal cell carcinoma, and to better understand the role of nephrectomy after nivolumab treatment.

Project description:BackgroundMicrophthalmia-associated transcription factor/transcription factor E (MiTF/TFE) translocation renal cell carcinoma (RCC) is a rare type of non-clear cell RCC (nccRCC), which is more common in females. Currently, there is no standardized treatment for advanced metastatic microphthalmia translocation RCC (MiT-RCC). The main treatment modalities include surgery, chemotherapy, immunotherapy, anti-vascular endothelial growth factor or vascular endothelial growth factor receptor (VEGFR) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and targeted therapy against the mesenchymal-epithelial transition (MET) factor signaling pathway.Case descriptionWe present the case of an 8-year-old male patient with hematuria and paroxysmal urinary pain. Based on tumor genetic testing results and targeted drug matching analysis, the patient underwent tumor biopsy, tumor radical surgery with vascular osteotomy, and cervicothoracic lymph node dissection. The patient was then treated with a combination of immunotherapy [sintilimab, a drug directed against programmed cell death receptor-1 (PD-1)] and VEGFR tyrosine kinase inhibitor (TKI) (from pazopanib to sunitinib). Throughout the 10 cycles of conventional chemotherapy (seven courses of sintilimab since the start of the third chemotherapy treatment), the patient's condition remained stable, with no tumor recurrence at the primary site. However, in the later stages, the patient developed a large amount of ascites, and the family requested discontinuation of treatment, ultimately leading to the patient's death.ConclusionsIn this case report, we summarize the therapeutic strategy of a young patient with metastatic transcription factor E3 (TFE3) MiT-RCC. For this disease, early immunotherapy and the use of precision-targeted drugs may have a favorable impact on the survival prognosis of the patient but may still be of less benefit in children with advanced multiple metastases. Therefore, further research on tumor driver genes, among other treatment components, is urgently needed to improve precision therapy.

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Complete response to perioperative treatment using nivolumab for metastatic renal cell carcinoma: A case report.

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Complete response to perioperative treatment using nivolumab for metastatic renal cell carcinoma: A case report.

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