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Metastatic Uveal Melanoma - Crossref

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Last Updated: 03 February 2022

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Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

Many patients with uveal melanoma have limited systemic treatment options, and re-induction with immune checkpoint blockade must be considered in many patients with uveal melanoma. From German skin cancer centers and the German national skin cancer registry, a total of 177 patients with metastatic UM treated with ICB were included. Patients who underwent ICB re-induction were compared to those who received only one treatment line of ICB vs. others who received just one treatment line of ICB were compared to those who received at least one ICB re-induction. Patients receiving ICB after re-induction had similar response rates than those receiving ICB.

Source link: https://doi.org/10.3390/cancers14030518


Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience

Percutaneous hepatic perfusion provides high-dose melphalan to the liver while minimizing systemic risk by filtering the venous hepatic blood. This two-center research sought to investigate the risks, tolerance to treatment, and survival of patients with hepatic-dominant metastatic uveal melanoma treated with PHP. PFS was 12. 4 months when initial PHP was launched, median hepatic PFS was 12. 4 months, and median OS was 18. 4 months. There were four cases of ischemic stroke and one patient with central pulmonary embolism in Cardiovascular events, as well as one patient with central pulmonary embolism. In conclusion, PHP is a safe and effective salvage therapy for liver-dominant metastatic uveal melanoma.

Source link: https://doi.org/10.3390/cancers14010118


Phase II Trial of Bevacizumab in Combination With Temozolomide as First-Line Treatment in Patients With Metastatic Uveal Melanoma

Abstract Lessons Learned is a student at the University of On the poor prognosis of this rare disease and because its biology is distinct from that of cutaneous melanoma. Bevacizumab was not present in vitro growth and in vivo hepatic metastasis of ocular melanoma cells in experimental models. Additional preclinical data showed a potential benefit when combining bevacizumab with dacarbazine, which indicates a potential benefit. In 36 patients with metastatic uveal melanoma, a noncomparative phase II study investigated a combination of bevacizumab with temozolomide in 36 patients with metastatic uveal melanoma. At least ten of 35 patients were required to have a predetermined PFR at 6 months rather than 40% using a modified 2-step Fleming scheme. Liver perfusion CT imaging was not effective in determining tumor response, and VEGF-A gene polymorphisms were not correlated with disease or survival. A 3-month PFR of 23% was seen in patients with MUM.

Source link: https://doi.org/10.1634/theoncologist.2015-0501


Combination of Immune Checkpoint Inhibitors and Liver-Specific Therapies in Liver-Metastatic Uveal Melanoma: Can We Thus Overcome Its High Resistance?

Uveal Melanoma is a rare disease, but it is the most common primary intraocular malignant tumor in adults. In contrast to the dramatic benefits of immunotherapy in several tumor types, as seen in cutaneous melanoma, immune checkpoint inhibitors did not achieve comparable results in Metastatic UM. Our results revealed a significant survival difference between Cohort 1 and Cohort 2, suggesting that this combination may extend the effectiveness of immunotherapy and consequently provide a survival benefit.

Source link: https://doi.org/10.3390/cancers13246390


Systemic and liver-directed therapies in metastatic uveal melanoma: state-of-the-art and novel perspectives

Metastatic uveal melanoma is the most common form of noncutaneous melanoma. Despite groundbreaking advances in the treatment of cutaneous melanoma, there have been few developments in the treatment of MUM, and no standard treatments for MUM have been established. Although the results in this setting have been disappointing so far, trials into novel immunotherapeutic regimens alone and in combination with targeted agents and liver-directed therapies are ongoing.

Source link: https://doi.org/10.2217/fon-2021-0318


868 Overall survival on tebentafusp in metastatic uveal melanoma (mUM) across the range of tumor gp100 expression levels

Background Tebentafusp is a TCR–anti-CD3-targeted fusion protein that targets melanoma-expressed gp100 antigen and has shown survival benefit in a randomized phase 3 trial of metastatic uveal melanoma. 1 2 In phase 2 and 3 trials enrolling late-stage mUM patients, we investigated correlations between gp100 expression in the tumor and pharmacodynamic response, as well as clinical outcomes on tebentafusp. After three doses of tebentafusp, a RNAseq analysis was used to determine association between baseline mRNA levels of gp100 and T cell infiltration and activation. IHC was distributed in both studies, with median H-Scores of 170 and 155. High baseline gp100 mRNA levels were consistent in archival and fresh tumor biopsies, with a 2-fold rise in CD3 and CD8 cell infiltration on tebentafusp, compared to little or no change in the gp100 low group. Expression changes in tebentafusp were also observed across a variety of gp100 expression levels. In gp100 high and low patient groups, the acute pharmacodynamic reaction to tebentafusp includes greater T cell infiltration and activation in the tumor microenvironment, according to Abstract 868. Table 1 TS and OS In gp100 high and low patient groups.

Source link: https://doi.org/10.1136/jitc-2021-sitc2021.868


538 Updated survival of patients with previously treated metastatic uveal melanoma who received tebentafusp

In a Ph3 trial, Background Tebentafusp, a bispecific fusion protein that combines an affinity-enhanced T cell receptor fused to an anti-CD3 antibody that can direct T cells to the target gp100+ cells, has shown an overall survival benefit for patients with untreated metastatic uveal melanoma. Metastatic uveal melanoma is a rare malignant tumor with 1-year, 2-yr, and 9% respectively, with a median OS of 7. 8 months in 2L+ patients. In the first analysis of the phase 2 IMCgp100–102 study, patients with previously treated mUM were 62% with median OS of 16. 8 months. Patients were dosed with tebentafusp every week, following intra-patient dose increase: 20 million mg dose 1, 30mcg dose 2+ and 68 mg dose 3+. Median OS remained unchanged at 16. 8 mos, with median duration of therapy ranging from 16. 8 mos to 5. 6 mos. 236 Figures from this 2-yr follow-up to IMCgp100-102 Conclusions This is the longest follow-up to a soluble TCR therapeutic's longest follow-up to date. Figure 1 This report provides the longest follow-up of OS and safety of a soluble TCR therapeutic. With a predicted 2-yr OS rate of 37 percent, Tebentafusp's survival for 2L+ mUM patients showed promising longevity for 2L+ mUM patients. A systematic review and meta-analysis of survival after metastatic uveal melanoma therapy. Patients with metastatic uveal melanoma undergoing treatment are enrolled in a phase II, multi-center research to determine the safety and effectiveness of tebentafusp in patients with metastatic uveal melanoma.

Source link: https://doi.org/10.1136/jitc-2021-sitc2021.538


Development of a Metastatic Uveal Melanoma Prognostic risk Score (MUMPS) for use in patients receiving immune checkpoint inhibitors

Abstract Background: Metastatic uveal melanoma is a rare disease for which no systemic therapy has demonstrated general survival benefit. There are no clear studies on prognostic factors for OS in patients with mUM treated with immune checkpoint inhibitors, but there are no reliable studies on prognostic factors for OS. This report looks at the characteristics of ICI benefit in patients with mUM. Methods We conducted a single-center retrospective cohort study of patients with mUM who received anti-PD1/L1 +/-anti-CTLA4 ICI between 2014 and 2020. Multiple cohort-free survival and OS were found between groups, and it was necessary to determine clinical correlates associated with ICI findings. We found 71 mUM patients with 75 lines of ICI therapy, according to the researchers. 53% of patients had stage IV disease within our cohort, 53% of whom had stage IV disease 2 years after they were first diagnosed. Patients were divided into three MUMPS risk groups based on the number of the above-mentioned prognostic factors: poor risk, Intermediate risk, and Good risk. P 0. 0001. Good risk patients had longer cPFS and OS than those with intermediate and poor risk disease; Conclusion We created a MUMPS risk score based on retrospective results that is made up of three commonly available clinical variables. This MUMPS risk score has a potential prognostic value. This MUMPS risk score has the potential prognostic value. In selecting ICI treatment administration for mUM, further verification in independent datasets is needed to determine the role of this MUMPS risk score in selecting ICI treatment management for mUM.

Source link: https://doi.org/10.1101/2021.02.28.21252611


Immediate results of treatment of patients with metastatic uveal melanoma using isolated liver chemoperfusion. The first domestic experience

Uveal melanoma is the most common primary intraocular tumor in adults. According to various researchers, the median survival of patients with liver metastases is 4 to 9. And the end of therapy is extremely poor, unlike the case of skin melanoma therapy. Patients with uveal melanoma metastatic to the liver are treated with isolated hepatic perfusion techniques, with the intention of evaluating the immediate results of the treatment. Local therapy is particularly interesting considering the possibility of developing a metastatic liver disease in patients with uveal melanoma. This article discusses the findings of ten metastatic melanoma patients' Isolated Hepatic Perfusion Therapy. A month after nine patients underwent IHP showed an effective response to therapy in 6 patients, a month after nine patients underwent IHP showed an objective response to therapy. According to the standard procedure, isolated liver chemoperfusion in a small group of patients allowed for an immediate response in 67% of cases.

Source link: https://doi.org/10.21518/2079-701x-2021-20-117-123


Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma

Since DDR1 was found to be overexpressed in UM cell lines and specimens, and widespread pathological deposition of extracellular matrix collagen, a form of DDR1 ligand, was demonstrated in liver microenvironment, thus encouraging metastatic colonization in liver. DDR1 marketed these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver, according to We tested this hypothesis and found that DDR1 supported these malignant cellular phenotypes and enabled metastatic colonization of UM in liver. Mechanistically, UM cells secretly secreted TGF-1, which converted quiescent hepatic stellate cells into energized HSCs that secretly expressed collagen type I. In conclusion, targeting DDR1 signaling and TGF- signaling may be a novel way to reduce hepatic metastasis in UM.

Source link: https://doi.org/10.1038/s41392-021-00563-x

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions