Emerging biological therapies for the treatment of malignant pleural mesothelioma

ABSTRACT

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.

Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.

Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.

KEYWORDS:

• Chimeric antigen receptor (CAR) T cells
• dendritic cell therapy
• immune checkpoint inhibitors
• immunotherapy
• malignant pleural mesothelioma (MPM)
• mesothelin
• tumor treating fields

List of Abbreviations

BAP1 – BRCA associated protein 1

BRCA – Breast cancer associated gene

BSC – Best Supportive Care

CAR-T – Chimeric Antigen Receptor T cells

CDK – Cyclin dependent kinase

CLS - Capillary leak syndrome

CTLA4 - Cytotoxic T-lymphocyte-associated protein 4

DC – Dendritic cells

EGFR – Epidermal Growth Factor Receptor

EPP - Extra-pleural pneumonectomy

FDA - Food & Drug Administration

ICI – Immune Checkpoint Inhibitors

miRNA – Micro ribonucleic acid

MPM – Malignant pleural mesothelioma

MSLN – Mesothelin

NSCLC – Non small cell lung cancer

OS – Overall Survival

PARP - Poly(adenosine diphosphate-ribose) polymerase

PD-L1 - Programmed Death Ligand 1

PFS – Progression Free Survival

rAd - Replication deficient adenoviruses

TAAs – Tumor Associated Antigens

TTFields – Tumor Treating Fields

USA – United States of America

VEGF - Vascular Endothelial Growth Factor

Declaration of interest

N Pavlakis sits on advisory boards for Boehinger, MSD, Merck, BMS, Astra Zeneca, Takeda, Pfizer, Roche & Ipsen. NP has speaking honoraria with Boehringer, Bayer, Novartis, Pfizer, Roche, Takeda & Ipsen. NP research institution receives funding from Bayer, Pfizer and Roche. S Kao receives honoraria from Astra Zeneca, Roche, Boehinger, Pfizer, BMS, MSD & Takeda. Astra Zeneca provides research funding to SKs institution. SK has received reimbursement for travel & accommodation from BMS, Roche & Boehringer. M Boyer has disclosures from Amgen, BMS, MSD, Pfizer, Genentech/Roche, Astra Zeneca, Novartis, Immugene, Earli & Eli Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.