Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience

Abstract

Background. Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4–15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed. Patients and Methods. This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints. Objective. To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors. Results. The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55–77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression. Conclusion. We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM.

The Role of Immune Checkpoint Blockade in Uveal Melanoma

“…A high number of patients developed severe ICB-related AEs of grade 3 (24 patients, 37.5%) and grade 4 (1 patient, 1.6%) [130]. Furthermore, Karivedu et al [131] published a retrospective analysis of eight metastatic UM patients who were treated with transarterial chemoembolization (TACE) and a combined ICB with nivolumab and ipilimumab. The median OS was 14 months and the median PFS was not reported.…”

“…Four patients developed treatment-related colitis; however, the severity of the AEs was not clearly reported. [131]. In a retrospective population-based study, Bol et al [115] evaluated the efficacy of a combined therapy with ipilimumab and nivolumab in 19 patients.…”

Uveal melanoma: progress in molecular biology and therapeutics

“… 219 – 221 Analysis of eight cases enrolled in a single-center trial indicated that metastatic UM patients treated with the combination of nivolumab and ipilimumab through transarterial chemoembolization (TACE) had a 25% PR rate and 50% SD rate. 222 A largescale phase II trial, GEM1402, was conducted with the combination of ipilimumab + nivolumab in a group of 50 metastatic UM patients. The ORR and SD rates were 12% and 52%, respectively [ClinicalTrials.gov identifier: NCT02626962].…”

Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study

“…In cutaneous melanoma, combined checkpoint blockade with ipilimumab and nivolumab revealed response rates and survival outcomes superior to PD-1 inhibitor monotherapy, albeit at the cost of high immune-related toxicity [10]. However, the significance of combined checkpoint blockade in UM is unclear and has only been investigated in case reports and small case series [6,11,12]. In this study, we evaluate the clinical course of 64 patients with metastatic UM who received combined checkpoint blockade.…”