Abstract
Immune checkpoint inhibitor (ICI) is a revolutionary breakthrough in the field of cancer treatment. Because of dysregulated activation of the immune system, patients with autoimmune disease (AID) are usually excluded from ICI clinical trials. Due to a large number of cancer patients with preexisting AID, the safety and efficacy of ICIs in these patients deserve more attention. This review summarizes and analyzes the data regarding ICI therapy in cancer patients with preexisting AID from 17 published studies. Available data suggests that the efficacy of ICIs in AID patients is comparable to that in the general population, and the incidence of immune-related adverse events (irAEs) is higher but still manageable. It is recommended to administer ICIs with close monitoring of irAEs in patients with a possibly high benefit-risk ratio after a multidisciplinary discussion based on the patient’s AID category and severity, the patient’s tumor type and prognosis, alternative treatment options, and the patient’s intention. Besides, the prevention and management of irAEs in AID patients have been discussed.
Highlights
The approved immune checkpoint inhibitors (ICIs) mainly involve several immune checkpoint– directed antibodies targeting cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1)
In the studies on the use of ICIs in cancer patients with unlimited tumor types and preexisting Autoimmune diseases (AIDs), the majority of malignant tumor types were still melanoma and/or non–small cell lung cancer (NSCLC) (Table 1) [34,35,36,37,38,39,40] Danlos et al [34] analyzed data from a large prospective study of anti-PD-1 treatment and found that the 45 patients with AID had no significant difference in objective response rate (ORR) or median overall survival (mOS) compared with those without AID, but the median immune-related adverse events (irAEs)-free survival time was significantly shorter (5.4 versus 13.0 months, p = 0.0002) and the incidence of total irAEs (TirAEs) was higher in patients with AID (44% versus 29%)
The results of the existing retrospective studies seemed to support that the efficacy of ICIs in patients with preexisting AID was comparable to that in the general population, and while the incidence of irAEs was higher, most irAEs were mild and manageable
Summary
The approved immune checkpoint inhibitors (ICIs) mainly involve several immune checkpoint– directed antibodies targeting cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1). CTLA-4 inhibits an immune response in several ways, including hindering autoreactive T-cell activation at a proximal step in the immune response, typically in lymph nodes [1, 2]. The PD-1 pathway regulates T cells at a later stage of the immune response, typically in peripheral tissues [3]. Differing from traditional chemotherapy and targeted therapy, ICI can break the state of immune tolerance in the tumor microenvironment (TME) and activate the body’s anti-tumor immunity. Autoimmune diseases (AIDs) represent a family of at least 80 diseases that share a common pathogenesis: an improper activation of the immune system attacking the body’s own organs [5]
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