New combination treatment for eye melanoma increased patient survival

Immune profiles of pre- and post-treatment (1 cycle) blood samples. Flow cytometric analysis of changes in the circulating cell population of shorter and longer survivors after treatment with a–c entinostat and pembrolizumab. The gating strategy is shown in Supplementary Figure 5. (A) Graph showing the frequency of CD3 + lymphocytes (left), CD14 + monocytes (center), and CD33 + neutrophils (right). (B) One cycle of longer (n = 12) survival before (circle) or after (square) treatment. (C) Analysis of CD8 + cytotoxic T cells in patients with shorter and longer survival times. Statistical analysis was performed using multiple paired t-tests for multiple comparisons using a two-step step-up (Benjamini, Krieger, and Yekutieli), among all groups in (a–b). The test was done. * Indicates the adjusted p-value.

Once it spreads, uveal (intraocular or ocular) melanoma (an abnormal form of cancer) shows a very high mortality rate.In a study published in Nature CommunicationsResearchers and physicians at Gothenburg University and Saar Glenska University Hospital show that new combination therapies may result in tumor shrinkage and prolonged survival in a small group of patients with metastatic uveal melanoma. I am.

Uvea melanomaRare forms of malignant melanoma begin with pigment cells in the eye rather than the skin. For cutaneous melanoma, immunotherapy with “checkpoint inhibitors” has often proven to be effective, but it has not been applied to intraocular melanoma.About 80 people Uveal melanoma Every year in Sweden, half of them often metastasize to the liver.Patient Metastatic uveal melanoma Often, they die shortly after diagnosis.

Clinical trial

This is because 29 patients with metastatic melanoma each received a combination of two inhibitors targeting HDAC (histone deacetylase) and PD-1 (checkpoint protein on T cells) II. This is a phase test. In four of these patients, the tumor shrank significantly, and in some patients the course of the disease was delayed. Unusually, three years after the study began, some patients are still alive today.

“Our hope was that HDAC inhibitors could reprogram hidden cancer cells so that they could be detected by immune cells, making immunotherapy with PD-1 inhibitors effective,” said a senior at Gothenburg University. Instructor and specialist Lars Ni explains. Majored in oncology at Sahlgrenska University Hospital.

“Overall, clinical trials have met our expectations, but they also don’t seem to be curative treatments. We did a genetic analysis to find out why there was a big difference in patient response. Jonas Nilsson, a professor at the Sahlgrenska Academy at Gothenburg University, said these treatments are active in both the Sahlgrenska Center for Cancer Research and the Harry Perkins Institute of Medical Research in Perth, Australia.

The researchers are now continuing to investigate why loss of the BAP1 gene causes resistance to immunotherapy and what other changes in blood composition may predict subsequent improvement in survival. Is Immunotherapy Patients with uveal melanoma.

Researchers identify promising drug combinations for melanoma

For more information:
Lars Ny et al, PEMDAC Phase 2 trial of pembrolizumab and entinostat in patients with metastatic uveal melanoma, Nature Communications (2021). DOI: 10.1038 / s41467-021-25332-w

Quote: Clinical trial: New combination therapy for ocular melanoma improved patient survival (August 27, 2021). Obtained from August 27, 2021

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