Abstract
Tumor-infiltrating T cell rescue by programmed cell death receptor-1 (PD-1)/PD-1 ligand-1 (PD-L1) immune checkpoint blockade is a recommended treatment for malignant diseases, including metastatic non-small-cell lung cancer (mNSCLC), malignant melanoma (MM), head and neck, kidney, and urothelial cancer. Monoclonal antibodies (mAbs) against either PD-1 or PD-L1 are active agents for these patients; however, their use may be complicated by unpredictable immune-related adverse events (irAEs), including immune-related pneumonitis (IRP). We carried out a retrospective multi-institutional statistical analysis to investigate clinical and biological parameters correlated with IRP rate on a cohort of 256 patients who received real-world treatment with PD-1/PD-L1 blocking mAbs. An independent radiological review board detected IRP in 29 patients. We did not find statistical IRP rate correlation with gender, tumor type, specific PD-1 or PD-L1 blocking mAbs, radiation therapy, inflammatory profile, or different irAEs. A higher IRP risk was detected only in mNSCLC patients who received metronomic chemotherapy +/− bevacizumab compared with other treatments prior PD-1/PD-L1 blockade. Moreover, we detected a strong correlation among the IRP rate and germinal expression of HLA-B*35 and DRB1*11, alleles associated to autoimmune diseases. Our findings may have relevant implications in predicting the IRP rate in mNSCLC patients receiving PD-1/PD-L1 blockade and need to be validated on a larger patient series.
Highlights
Immune checkpoint blockade with monoclonal antibodies to programmed cell death receptor-1 (PD-1) and progressive disease (PD)-1 ligand-1 (PD-L1) alone or in combination with chemotherapy, radiotherapy, or bevacizumab is an expanding treatment strategy for metastatic non-small-cell lung cancer, malignant melanoma, head and neck cancer, kidney and urological cancer, and other common malignancies.These innovative immune-oncological treatments are leading to positive results in terms of clinical benefit and survival in these patients worldwide [1,2,3]; this therapeutic approach can be complicated by a number of immune-mediated adverse events that are mostly unpredictable, and require intensive medical intervention and sometimes lead to real-life-threatening situations
189 patients received nivolumab as a therapy for metastatic disease, 29 patients were treated with pembrolizumab
We found a trend to a prolonged survival that, did not reach statistical significance
Summary
Immune checkpoint blockade with monoclonal antibodies (mAbs) to programmed cell death receptor-1 (PD-1) (nivolumab and pembrolizumab) and PD-1 ligand-1 (PD-L1) (atezolizumab, avelumab, and durvalumab) alone or in combination with chemotherapy, radiotherapy, or bevacizumab is an expanding treatment strategy for metastatic non-small-cell lung cancer (mNSCLC), malignant melanoma, head and neck cancer, kidney and urological cancer, and other common malignancies These innovative immune-oncological treatments are leading to positive results in terms of clinical benefit and survival in these patients worldwide [1,2,3]; this therapeutic approach can be complicated by a number of immune-mediated adverse events (irAEs) that are mostly unpredictable, and require intensive medical intervention and sometimes lead to real-life-threatening situations. It shows a higher frequency in patients who receive combination therapies compared to single agent-based therapy and may be severe (grade 3-4) in 15–20% of the cases [7,8]
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