Impact of Cytoreductive Nephrectomy Following Nivolumab Plus Ipilimumab Therapy for Patients With Advanced Renal Cell Carcinoma.

BACKGROUND/AIM: CheckMate 214 study revealed that nivolumab plus ipilimumab combination therapy showed a strong and durable effect compared to sunitinib for patients with advanced renal cell carcinoma (aRCC). Most of the patients underwent previous nephrectomy before systemic treatment. We retrospectively investigated the clinical outcomes of Japanese patients treated with cytoreductive nephrectomy following nivolumab plus ipilimumab for aRCC. PATIENTS AND METHODS: Seventy-nine patients were treated with systemic therapy for aRCC between October 2018 and August 2021 at the Saitama Medical University International Medical Center. Ten of 61 patients treated with nivolumab plus ipilimumab underwent cytoreductive nephrectomy after the combined immunotherapy. RESULTS: The median overall survival and progression-free survival were 24.3 and 15.9 months, respectively. The objective response rate was 50.8%; 9.8% of patients had a complete response, and the median time to objective response was 3.2 (range=1.3-19.7) months. The estimated percentage of patients who sustained an objective response at 30 months was 73.0%. Twenty-three patients (74%) in the complete or partial response (CR/PR) group, 11 patients (52%) in the stable disease (SD) group, and two patients (22%) in the progressive disease (PD) group had immune-related adverse events of grade 3 or higher, respectively. For all 10 patients, cytoreductive nephrectomy following nivolumab plus ipilimumab treatment were completed safely. Three patients achieved a pathological complete response without viable cancer cells. Only two patients had residual lesions on images after deferred cytoreductive nephrectomy; the remaining patients achieved radiological CR. CONCLUSION: Cytoreductive nephrectomy after nivolumab plus ipilimumab treatment could be useful in a limited number of cases, possibly resulting in curative nephrectomy due to the durable therapeutic effect of immunotherapy.

Efficacy of Nivolumab Plus Ipilimumab in a Patient With Renal Cell Carcinoma Concomitant With Cardiac Metastasis: A Case Report.

BACKGROUND/AIM: Patients with metastatic renal cell carcinoma (RCC) with cardiac metastasis have had poor outcomes in the era of molecular targeted therapy. There are few reported outcomes for patients with cardiac metastasis of RCC treated with immune checkpoint inhibitors (ICIs). CASE REPORT: A 32-year-old female presented with metastatic RCC (unclassified type) with contralateral renal and cardiac metastases, as well as renal hilar lymph node metastases (cT4N2M1). An 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomographic (CT) scan was useful in diagnosing cardiac metastasis. Nivolumab plus ipilimumab achieved prominent shrinkage of almost all tumors except for one cardiac tumor. FDG-PET/CT scan also revealed the marked attenuation of FDG uptake in each tumor. In addition, a needle biopsy of the remaining primary renal tumor was pathologically observed to have no viable cancer cells. CONCLUSION: This successful case suggests that ICIs might provide a better outcome even for patients with cardiac metastasis of RCC, and that FDG-PET/CT scan might be useful for therapeutic assessment, as well as diagnosis.

Serum Lactate Dehydrogenase Before Nivolumab Treatment Could Be a Therapeutic Prognostic Biomarker for Patients With Metastatic Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: The purpose of this retrospective study was to identify the predictive biomarkers of response to pretreatment for patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. MATERIALS AND METHODS: The subjects were 54 patients treated with nivolumab for mRCC with a clear cell component (mccRCC) between September 2016 and February 2018. We analyzed the impact of serum biomarkers (lactate dehydrogenase [LDH], neutrophil-to-lymphocyte ratio, and C-reactive protein) on patients treated with nivolumab. We adopted the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model using six clinical factors (0=favorable, 1 or 2=intermediate, 3 to 6=poor risk groups, respectively). RESULTS: The prognostic risk classification (non-poor vs. poor) and serum LDH levels were correlated with the objective response of nivolumab treatment for mccRCC. Elevated serum LDH levels at baseline were an independent biomarker for progression-free survival (PFS) of mccRCC patients receiving nivolumab [HR=2.268 (95%CI=1.014-5.051), p=0.046]. Notably, high LDH levels were associated with a poorer PFS for patients in the favorable-risk group. CONCLUSION: Serum LDH levels at baseline before nivolumab treatment were associated with the objective response and clinical outcome of nivolumab treatment.