The Evolving Therapeutic Landscape for Malignant Pleural Mesothelioma

Abstract

Purpose of review: For patients with malignant pleural mesothelioma, prognosis is poor with extremely low 5-year survival rates and limited therapeutic options. Here, we review the current treatment landscape for mesothelioma and highlight promising future therapeutic directions.

Recent findings: Evolving frontline therapeutic options for mesothelioma include VEGF inhibition in combination with chemotherapy and dual immune checkpoint inhibition, with synergisms between the therapies and response prediction via biomarkers also being explored. Evolving experimental treatments for mesothelioma include PARP and ALK inhibitors, dendritic and CAR T-cell therapies, anti-mesothelin vaccines, and oncolytic viral therapies, representing timely advances in the field. The therapeutic landscape for malignant pleural mesothelioma is evolving and preferred treatment in the frontline and later settings will likely evolve with it. However, this does not preclude the evidence for including multi-modal therapies spanning angiogenesis and immune checkpoint inhibitors, and biomarker utilization, in current clinical trials and management.

Keywords: CAR T-cell therapy; Genetic targets; Immunotherapy; Malignant pleural mesothelioma; Mesothelioma biomarkers; VEGF inhibition.

Figure 1.

Treatment Response in a 61 year old Male Patient with Malignant Pleural Mesothelioma, Biphasic type, on Dual Immune Checkpoint Inhibitor (ICI) Therapy A. Pre-treatment computed tomography (CT) chest at time of diagnosis shows a nodular pleural tumor in the right hemithorax. The tumor encased the lung from the apex to costophrenic angles with thickness greater than 2cm in some areas, and nodular tumor directly invading mediastinal fat. B. Pre-treatment positron emission tomography–computed tomography (PET-CT) following diagnosis of mesothelioma shows extensive hypermetabolic pleural-based soft tissue nodularity throughout the right hemithorax including the fissures and mediastinal fat. C. Post-treatment CT chest, after four months of dual ICI therapy with Nivolumab 360mg every 3 weeks and Ipilimumab 1mg/kg every 6 weeks demonstrates that the previously extensive right sided pleural nodularity has significantly decreased and is now barely apparent. This patient’s presenting symptoms of dyspnea and chest wall pain resolved and he felt well overall. Treatment was complicated by acute kidney injury that was attributed to ICI-induced nephritis and improved with oral steroids.