Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the approval of first-line treatment with ICI was analyzed. A partial response to first-line treatment was observed in 7% of patients treated with anti-programmed cell death protein (PD)-1 monotherapy and in 21% with combined anti-cytotoxic T lymphocyte antigen (CTLA)-4 plus anti-PD-1 therapy. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.5 months in the post-ICI era (hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.28-0.67; p < 0.001). The estimated one-year overall survival rate increased from 25.0% to 41.9% and the median overall survival improved from 7.8 months to 10.0 months, respectively (HR 0.52; 95% CI 0.34-0.79; p = 0.003). Thus, the introduction of ICI as first-line treatment appears to have significantly improved the real-world survival of patients with metastatic UM, despite relatively low response rates compared to cutaneous melanoma. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM.

[Immunosuppressive treatment of the myelodysplastic syndrome]. / Immunosuppressiv behandling af det myelodysplastiske syndrom.

INTRODUCTION: The myelodysplastic syndrome (MDS) is featured by cytopenia in one or more cell lineages. Until recently the only possible treatment was supportive care with transfusions and antibiotics, but new options have now become available. In this article the results of immunosuppressive treatment are described and discussed. MATERIAL AND METHODS: We present seven patients who were treated with antithymocyte globulin (ATG) and cyclosporine. Previous series of patients with MDS treated with ATG are summarized. RESULTS: Two of the seven patients treated with ATG and cyclosporine achieved a complete response, one had a partial response and one had a minor response. DISCUSSION: In MDS an acquired insult to the hemopoietic stem cell leads to impaired differentiation and myelodysplasia. A model of MDS pathophysiology suggests that transformation of normal stem cells induces an autoimmune T cell response with the bone marrow as the target organ. This autoimmune attack results in chronic overproduction of pro-apoptotic cytokines, especially TNF-alpha. This may contribute to a dysplastic morphology and increased apoptosis in the marrow. It is suggested that the mechanism of action of ATG in MDS may involve elimination of CD8+ lymphocyte mediated suppression of granulocyte/monocyte progenitor cells.

[Asystole following synchronized DC conversion]. / Asystoli efter synkroniseret DC-konvertering.

A case of asystole following direct current CDC cardioversion for atrial fibrillation is described and studies of the complications associated with DC cardioversion are presented. It is important to be aware of the possible severe complications of DC cardioversion.