Dual immunotherapy with nivolumab and ipilimumab for metastatic melanoma: Real-world outcomes from a single-center study.

Abstract

e21541 Background: This study evaluates the efficacy and safety of dual immunotherapy with nivolumab and ipilimumab in patients with metastatic melanoma. Conducted at Moscow City Oncology Hospital No. 62 between Sept. 2015 and Oct. 2023, the analysis includes 205 patients with a median follow-up of 18.2 months (range: 0.1–110 months; interquartile range: 6.7–30.4 months). Methods: Patients received nivolumab and ipilimumab as part of systemic therapy for metastatic or unresectable melanoma. Clinical and demographic characteristics, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier curves and Cox regression models to evaluate prognostic factors. Confidence intervals (95% CI) were provided for all estimates. Results: The median age was 55 years (range: 19–84). The majority had cutaneous melanoma (81.5%), with 33.7% presenting brain metastases and 70.7% with visceral metastases. BRAF mutations were identified in 53.2% of patients, and 26.3% had elevated baseline lactate dehydrogenase (LDH). The median PFS was 7.9 months (95% CI: 4.2–11.5), with 1-, 2-, 3-, and 5-year PFS rates of 43%, 33%, 30%, and 21%, respectively. The median OS was not reached; 1-, 2-, 3-, and 5-year OS rates were 74%, 60%, 55%, and 50%, respectively. The objective response rate (ORR) was 45.8%, including a complete response (CR) in 15.1% and partial response (PR) in 30.7%. Stable disease (SD) occurred in 15.6%, while 38.5% experienced progression disease (PD). Median PFS for CR was not reached; for PR, it was 26.6 months (95%CI: 0.1–54.8); for SD 11,5 months (95%CI: 8,9-14,1) and for PD 2,5 months (95% CI: 2,0-3,0) . Median OS for CR and PR were not reached,for SD it was 45,3 months (95% CI not reached), for PD 11,2 months (95% CI: 4,9 - 17,4). Immune-related adverse events (irAEs) occurred in 59% of patients. Prognostic factors for improved PFS included the presence of irAEs (hazard ratio [HR] 0.66; 95% CI: 0.46–0.93; p = 0.019) and primary metastatic disease (HR 0.65; 95% CI: 0.43–0.98; p = 0.034). Brain metastases (HR 1.76; 95% CI: 1.23–2.53; p = 0.002) and prior anti-PD-1 therapy (HR 1.52; 95% CI: 1.02–2.26; p = 0.039) were associated with poorer PFS. Brain metastases also negatively impacted OS (HR 1.62; 95% CI: 1.03–2.54; p = 0.035). Factors such as female gender (HR 1.49; 95% CI: 0.95–2.35; p = 0.083) and presence of irAEs (HR 0.66; 95% CI: 0.42–1.04; p = 0.071) demonstrated a trend toward statistical significance in their impact on OS. Conclusions: Dual immunotherapy with nivolumab and ipilimumab demonstrates durable responses and favorable long-term survival outcomes in metastatic melanoma. Prognostic factors, including brain metastases and irAEs, significantly influence patient outcomes. This real-world data supports the continued use of dual immunotherapy in advanced melanoma, emphasizing the need for careful patient selection and management of adverse events.