Adverse Effects of Anti-PD-1/PD-L1 Therapy in Non-small Cell Lung Cancer

Abstract

Currently, immunotherapy has shown great efficacy in clinical trials, and monoclonal antibodies directed against immune checkpoint PD-1/PD-L1 have shown encouraging results in first-line or second-line treatment of non-small cell lung cancer patients. Meanwhile, anti-PD-1/PD-L1 immune checkpoint drugs combined with other treatments, such as chemotherapy, targeted therapy as well as anti-CTLA-4 checkpoint therapy, are considered an attractive treatment with higher efficacy. However, toxicity associated with PD-1/PD-L1 blockade is worth attention. Understanding the adverse effects caused by anti-PD-1/PD-L1 immunosuppressive agents is vital to guide the clinical rational use of drug. In this review, we summarized the adverse effects that occurred during the clinical use of anti-PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer and discussed how to effectively manage and respond to these adverse reactions.

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

“…Ophthalmoplegia was diagnosed at a median onset of 35 days. According to recent reviews on ocular adverse events, the average onset time of ophthalmoplegia was approximately 6 weeks after ICIs initiation (range 2–12 weeks) ( 19 , 89 – 91 ). The median interval between the onset of ICIs use and the diagnosis of dry eye was 6.5 months in 26 patients secondary to ICIs ( 24 ).…”

“…The most common reported manifestations of ICI-related MG are ptosis (75%), dyspnea (62%), limb weakness (55%), dysphagia (48%), and diplopia (42%) following ICI use ( 93 ). Severe muscle dysfunction with respiratory affectation, myocarditis, and/or myositis can also be detected in approximately two-thirds of individuals suffering from MG, and are the most fatal manifestations requiring mechanical support ( 89 , 93 ). Approximately 20% of the individuals could die of MG upon an increase in respiratory dysfunction ( 99 ).…”

“…Moreover, the proportion of grade 3-4 irAEs is higher with CTLA-4 inhibitors (31%), compared to PD-1 inhibitors (10%) ( 132 , 134 ). Data from a recent clinical trial reported on lower overall incidence of AEs in monotherapy with ICIs than that of combination therapy in NSCLC ( 89 , 135 ). Furthermore, PD-L1 inhibitors combined with chemotherapy have a higher incidence of irAEs than monotherapy with PD-L1 inhibitors (98.2% vs .…”

“…Therapy with immunosuppressive and intravenous immunoglobulin or plasmapheresis have been found effective in a cohort of patients with MG ( 93 , 94 ). It could also be used in patients treated with corticosteroids who were still symptomatic or had contraindications to corticosteroids, and experienced severe side effects with advanced systemic affections ( 89 , 158 ). Suspending ICIs therapy is not necessary for the treatment of ophthalmoplegia in severe autoimmune MG ( 159 ).…”

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

“…Treatment options for people with lung cancer vary according to the type of lung cancer, stage of the disease and the patient’s functional status. Treatments can include surgical resection, chemotherapy, radiotherapy, targeted therapy and immunotherapy, which are physically and mentally invasive approaches [ 9 , 10 , 11 , 12 , 13 ]. Besides those treatments, non-surgical/pharmacological approaches are gaining growing attention as adjuvants in the therapy of lung cancer such as dietary plans and physical activity.…”