Mesothelioma is a rare type of cancer that affects the cells that make up a thin membrane around organs. Although this condition predominantly affects the lining of the chest wall, it can also affect the lining of the abdomen and the heart. The majority of cases of mesothelioma result from asbestos exposure. Treatment involves multiple modalities combining surgery, chemotherapy, and radiation. Despite treatment with a multimodal approach, the prognosis of mesothelioma is poor, with five-year mortality rates currently reported to be higher than 90%.
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Mesothelioma CT Courtesy of Dr. Frank Gaillard
Newer treatment modalities for mesothelioma are currently being researched. Drugs that bind to the protein on the surface of the cells called mesothelin have shown great promise in the treatment of this cancer. Drug LMB-100 has shown potential in boosting the immune system and shrinking mesothelioma tumors.
Research on LMB-100 for mesothelioma
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A study on ten patients has suggested that the drug LMB-100 could prolong the life of patients with advanced mesothelioma. Dr. Hassan and his team conducted a phase I trial to examine the safety and efficacy of the drug.
Methodology: All ten of the patients received an immune checkpoint inhibitor such as nivolumab or pembrolizumab, which helps the immune system target cancer cells.
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Findings: Some patients who received PD-1 inhibitor (pembrolizumab or nivolumab) after LMB-100 had an overall tumor response of 40%, and the median overall survival was 11.9 months. Therefore, patients with a combined treatment performed better than those with pembrolizumab/nivolumab alone. In addition, four of the ten patients responded to treatment, including one complete response and three partial responses.
Further studies were performed in mice that either received implants or grafts with human mesotheliomas. This yielded similar results in that the tumor response to therapy was greater in mice who received both LMB-100 and pembrolizumab compared to mice who only received one treatment option.
Due to the small nature of the study, it is hard to conclude whether patients were responding to the combination of the drugs or just to the agent pembrolizumab. Therefore, a larger study is currently underway to explore the combination of therapies for the shrinking of mesothelioma tumors in greater detail.
“Clinical outcomes from this study will help determine whether LMB-100 plus an immune checkpoint blockade is a valid treatment strategy for mesothelin-positive solid tumors,” said Raffit Hassan, M.D., Chief of the Thoracic and GI Malignancies Branch.
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References
Jiang, Q., et al. (2020). Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti–PD-1 antibody in patients with mesothelioma and mouse tumor models. Science Translational Medicine, 12(559), eaaz7252. https://doi.org/10.1126/scitranslmed.aaz7252
