The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review

Abstract

The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.

Keywords: Thymic tumors; clinical research; immunotherapy; systemic therapy.

Figure 1

Emerging biomarkers for response of thymic epithelial tumors to immune checkpoint inhibitors. PD-L1, programed death ligand-1; TCR, T cell receptor; irAEs, immune-related adverse events; *, tumor-related biomarker evaluation in prospective clinical trials is largely limited to thymic carcinoma.

Figure 2

Immune-related adverse events observed in patients with thymic epithelial tumors receiving immunotherapy. Immune checkpoint inhibition increases the risk for development of a wide spectrum of immune-related adverse events in patients with thymic epithelial tumors (30-33). A predisposition toward muscle and neuromuscular toxicity is observed, which can be severe and life-threatening. GI, gastrointestinal.