Case Report: A Case of Renal Cell Carcinoma Unclassified With Medullary Phenotype Exhibiting a Favorable Response to Combined Immune Checkpoint Blockade

Abstract

Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is an extremely rare variant of kidney cancer with poor prognosis. Recently, immune checkpoint inhibitors (ICIs) have been the mainstay of treatment for advanced clear cell renal cell carcinoma (RCC). However, the efficacy of ICI in the treatment of RCCU-MP remains unclear. Here, we report about a 63-year-old Japanese man who was referred to our hospital with a diagnosis of RCC of the left kidney with multiple–lymph node involvement (cT3aN1M1). The patient underwent nephrectomy with lymph node biopsy, which was histopathologically diagnosed as RCCU-MP. Thereafter, he received combined immune checkpoint blockade with nivolumab and ipilimumab. After induction therapy, follow-up computed tomography revealed shrinkage of the metastatic lymph nodes. Moreover, the patient was relieved of his subjective symptoms and his performance status improved. However, after 15 months, maintenance ICI therapy was discontinued because of disease progression, and the patient died 28 months after diagnosis. Longitudinal analysis of peripheral blood mononuclear cells revealed increased stem cell memory and central memory CD8+ T-cell subsets during response to therapy and enhanced expression of exhaustion markers on CD8+ T cells upon treatment resistance. Combined immune checkpoint blockade could be effective in the treatment of metastatic RCCU-MP.

Successful long-term management of metastatic clear cell renal cell carcinoma with nivolumab: a case report and literature review

“…However, due to intracardiac metastasis, the treatment was switched to nivolumab, resulting in a reduction in the size of the metastasis that remained stable for 12 months while continuing the nivolumab treatment [ 29 ]. Another case report described a patient who received treatment with a combination of nivolumab and ipilimumab, resulting in a partial response for 15 months [ 30 ]. However, after this period, the disease progressed, and the patient passed away [ 30 ].…”

“…Another case report described a patient who received treatment with a combination of nivolumab and ipilimumab, resulting in a partial response for 15 months [ 30 ]. However, after this period, the disease progressed, and the patient passed away [ 30 ]. The case presented adds to this limited evidence and represents, to the best of our knowledge, the longest documented OS in current literature for patients treated with nivolumab monotherapy for metastatic ccRCC that had previously progressed after two lines of systemic therapy.…”