A multireferral centre retrospective cohort analysis on the experience in treatment of metastatic uveal melanoma and utilization of sequential liver-directed treatment and immunotherapy

Abstract

Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed. In all, 18 patients in the series received sequential therapy. The median overall survival (OS) was 17 months (n=37), which compared favourably with previously reported series. Patients treated with TAC first or second line had an overall progression-free survival (PFS) of 9 months (n=29) and IT PFS 7 months (n=26). The overall response rate (ORR) for TAC first line was 26% and the disease control rate (DCR) was 65% (n=23). ORR for IT first line was 7%, DCR 77% (n=14). Second-line (cross-over) IT ORR was 16%, DCR 58% (n=12). For second-line (cross-over) TAC, ORR was 50% and DCR was 66% (n=6). Toxicity was manageable. There were no cases of autoimmune hepatitis. In this retrospective small series analysis in uveal melanoma, liver-directed therapy and IT in sequence have shown to be active and reasonably well tolerated. Further prospective clinical trials should clarify the role of these treatments and their potential survival benefit.

An Outcome Assessment of a Single Institution’s Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis

“…In fact, some of our liver-directed treatments have been performed with concurrent systemic immunotherapies. Itchins et al performed a small retrospective cohort analysis of 37 patients managed in tertiary referral centers and found that transarterial chemotherapy and immunotherapy in sequence have shown to be active and reasonably well tolerated [45]. In this regard, combination treatment with immunoembolization with immune checkpoint blockades (ipilimumab and nivolumab) [NCT03472586] and radioembolization with immune checkpoint blockades [NCT02913417] are under investigation at our institution and these studies would give us more insights in the mechanism of potential survival prolongation by addition of immune checkpoint blockades to liver-directed treatments.…”

The Role of Immune Checkpoint Blockade in Uveal Melanoma

“…Itchins et al [114] reported the results of a single-center cohort analysis on 37 metastatic UM patients who received a sequential therapy with transarterial chemotherapy (TAC), ICB (predominantly ipilimumab), and a systemic chemotherapy. Although the ORR was comparably poor, this combined approach led to the longest median PFS (9 months) and OS (17 months) among all therapies investigating ipilimumab.…”

“…Although the ORR was comparably poor, this combined approach led to the longest median PFS (9 months) and OS (17 months) among all therapies investigating ipilimumab. However, interpreting these results may be problematic, as the authors did not distinguish between different ICB antibodies when reporting the outcomes [114].…”

“…The median PFS was around 3 months and comparable among the different studies and antibodies. The longest median PFS of 9 months was achieved in a study investigating a treatment approach combining ICB, TAC, and systemic chemotherapy [114]. Throughout the studies, most of the responding patients achieved only a PR.…”

Novel Prognostic Immunohistochemical Markers in Uveal Melanoma-Literature Review

“…Studies with ipilimumab, tremelimumab, nivolumab, and pembrolizumab were somewhat disappointing [77][78][79][80][81][82][83]. Slightly better results were achieved in combination therapy in which drugs against both types of ICIs receptors were used: CTLA-4 and PD-1, but still without a satisfactory breakthrough [84,85]. Another group of biomarkers targeted for cancer therapy is RTKs: IGFR, EGFR VEGFR, c-Met, and its ligands.…”