Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma. Patients classified as intermediate- or poor-risk by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)—particularly those with multiple organ metastases—typically have an unfavorable prognosis. This report describes a 65-year-old man who developed multiple metastases to the lungs, liver, and bone shortly after undergoing radical nephrectomy for right-sided renal cancer. Baseline laboratory abnormalities included anemia, neutrophilia, and thrombocytosis. The patient’s IMDC score was 5, consistent with poor-risk disease.
The patient received first-line systemic therapy consisting of the programmed death-ligand 1 (PD-L1) inhibitor benmelstobart combined with the multi-target tyrosine kinase inhibitor anlotinib. Radiological assessment at 6 weeks demonstrated a partial response (PR), with an overall tumor reduction of approximately 48%. Subsequent imaging showed durable maintenance of the PR, accompanied by marked symptomatic improvement and better performance status.
During combined therapy the patient developed progressive proteinuria. The maximum recorded 24-hour urinary protein was 5.18 g. Clinicians implemented stepwise dose reductions of anlotinib in response to proteinuria, but the proteinuria recurred despite these measures. Given the persistence and severity of the renal adverse event, the TKI was ultimately discontinued. After stopping anlotinib the patient’s proteinuria notably improved.
Approximately three years into treatment, the patient experienced a gradual rise in serum creatinine to a peak of 228 μmol/L. The treating team considered the possibility of treatment-related renal toxicity as a contributor to the creatinine elevation. In the context of sustained disease control, immunotherapy with benmelstobart was discontinued at that time.
Following cessation of anlotinib, the patient continued benmelstobart monotherapy as maintenance treatment. The case documents sustained deep remission while on immunotherapy alone for an extended period after discontinuation of the TKI. This clinical course suggests that patients who achieve a strong response to combined anti-angiogenic and immune checkpoint blockade may retain durable disease control on maintenance immunotherapy after stopping TKIs for intolerable adverse events.
After benmelstobart was stopped due to rising serum creatinine, no further antitumor therapy was administered. The patient eventually experienced disease progression and died in September 2024. Overall survival from initial systemic therapy was 44 months.
This case provides several clinically relevant observations based on the authors’ report:
The combination of benmelstobart and anlotinib yielded a rapid and durable antitumor response in an IMDC poor-risk patient with multisite metastatic ccRCC, achieving a PR as early as 6 weeks and sustained tumor control.
Severe renal adverse events (progressive proteinuria and later creatinine elevation) occurred during combined targeted and immune therapy. Despite dose reductions of anlotinib, proteinuria recurred and required discontinuation of the TKI; renal function later worsened while on prolonged therapy.
Discontinuation of the TKI because of intolerable toxicity followed by maintenance immunotherapy alone was associated with continued deep remission for an extended interval, suggesting that durable antitumor immunity or tumor microenvironment remodeling induced by anti-angiogenic therapy may contribute to sustained benefit.
The case highlights the importance of vigilant renal monitoring during combined TKI and immune checkpoint inhibitor therapy and supports individualized treatment adjustment when significant toxicity arises.
Limitations: This is a single case report; findings describe one patient’s course and outcomes. Details beyond those reported in the source (such as additional laboratory trends, specific dosing schedules or management steps beyond dose reductions and discontinuation, biopsy or immunologic correlates) were not provided in the abstract and therefore are not reported here.
Overall, the case illustrates that in select patients with IMDC poor-risk ccRCC, combination anti-angiogenic therapy plus immunotherapy may produce rapid and long-lasting responses, but careful monitoring and individualized management of renal toxicity are essential.