Immunotherapy in malignant peritoneal mesothelioma (Review)

Abstract

Over the last decade, there has been a movement in cancer treatment away from cytotoxic therapies toward strategies that enhance the immune system against cancer. Immune checkpoint inhibitors (ICIs) have been incorporated into the treatment regimens for patients with various solid tumors. Mesothelioma trials revealed encouraging efficacy; however, patients with peritoneal mesothelioma are usually excluded, slowing the progress of improving the treatment of this aggressive cancer and compelling oncologist to rely on retrospective studies despite their flaws and limitations. Currently, there is no consensus on the role of ICIs in the treatment of malignant peritoneal mesothelioma (MPeM). The present review discusses data from clinical studies that examined immunotherapy in MPeM and evaluates what is known about the relevance of the tumor microenvironment and clinically validated biomarkers for ICIs efficacy. Furthermore, a proposed strategy for utilizing immunotherapy in treating MPeM is discussed. Contents1. Introduction 2. MPeM tumor microenvironment and clinically established biomarkers for immune checkpoint inhibitors (ICIs) efficacy 3. Immune checkpoint inhibitors in peritoneal mesothelioma 4. Future directions

A Complete Response to Pembrolizumab in Malignant Peritoneal Mesothelioma: A Case Report

“…However, the majority of MPeM cases are epithelial. Hence, these immunological and molecular differences between pleural and peritoneal mesothelioma hinder the extrapolation of any relevant findings [ 4 , 5 ].…”

“…The response rate was reported to be 16% in epithelioid, and it was noted that PDL1 expression was more common in the peritoneal subset with 25% of MPeM classified as having a tumor proportion score (TPS) greater than or equal to 50%. However, whether PDL1 expression is predictive of benefit remains unknown [5][6][7]. In another study, the clinical efficacy of immunotherapy in patients with advanced MPeM was evaluated, and an overall response rate of 19.2% and a median progression-free survival (PFS) of 5.5 months was reported [8].…”

Malignant Peritoneal Mesothelioma: An In-Depth and Up-to-Date Review of Pathogenesis, Diagnosis, Management and Future Directions

“…One of the most recent studies of immunotherapy in MPM was published in 2023, which reviewed the use of single or dual-agent immunotherapy or immunotherapy combined with chemotherapy. The authors concluded that due to the small number of patients with MPM in the clinical trials performed to date, no definitive conclusions could be reached, and therefore, no firm recommendations were made [85]. The authors proposed that given the lack of clear evidence regarding immune checkpoint inhibitors in comparison to chemotherapy as a first-line therapeutic choice for MPM, it would be reasonable to reserve them for use as a later option [85].…”

“…The authors concluded that due to the small number of patients with MPM in the clinical trials performed to date, no definitive conclusions could be reached, and therefore, no firm recommendations were made [85]. The authors proposed that given the lack of clear evidence regarding immune checkpoint inhibitors in comparison to chemotherapy as a first-line therapeutic choice for MPM, it would be reasonable to reserve them for use as a later option [85]. The use and outcome of molecular and immune therapy in MPM remain vastly unknown and are an extremely promising area of investigation for the future.…”

Major response of a peritoneal mesothelioma to nivolumab and ipilimumab: a case report, molecular analysis and review of literature

“…However, despite some studies reporting encouraging results, the efficacy of ICI in MPM has not been formally demonstrated due to the low number of MPM cases in clinical trials, which predominantly include MPlM. The molecular heterogeneity between MPM and MPlM also complicates the interpretation and extrapolation of results ( 1 , 2 , 6 , 7 ). Predictive biomarkers for response to immunotherapy in MPM are poorly defined.…”