Adverse Events Induced by PD-1/PD-L1 Inhibitors: A Real-World Single-Centre Experience with a Management-Based Approach

Abstract

Aim To assess the efficacy and tolerance of programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors and the impact of a standardised management-based protocol in a real-world setting. Patients and Methods Data from patients who had received anti-PD-(L)1 were collected from our pharmacy database. Clinical response and toxicity were assessed using RECIST criteria and CTCAE version 5.0, respectively. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan–Meier method. Potential prognostic factors were identified using Cox’s model. Results A total of 196 patients and 201 lines of treatment were included (median age: 66 (range: 38–89) years). Types of cancer included non-small cell lung cancer (73%), transitional cell carcinoma (10%), renal cell carcinoma (6%), small cell lung cancer (5%), head and neck squamous cell carcinoma (4%) and classical Hodgkin’s lymphoma (1%). Twenty-five (12%) patients had pre-existing autoimmune conditions. Our standardised management-based protocol included 129 (64%) patients. Objective response rate was 29%, median OS was 10 months (IQR: 7–15) and median PFS was 5 months (IQR: 1–22). Patients with an abnormal baseline complete blood count had a worse OS (HR=2.48 [95% CI: 1.24–4.96]; p=0.0103). Thirty-three (16%) patients experienced severe (grade 3 or 4) immune-related adverse event (irAE). There were three (1%) irAE-related deaths. AEs resolved faster when patients were assessed by an internist before anti-PD-(L)1 initiation (p=0.0205). Conclusion PD-1 and PD-L1 inhibitors are effective and safe in a real-world setting. Implementation of a standardised management-based protocol with internal medicine specialists is an effective way to optimise irAE management.

The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation

“…Furthermore, in a portion of patients, the ICB treatment can cause the immune system to attack healthy tissue (immune related adverse events, irAEs) and eventually leads to discontinuing the lifesaving treatment 5 . Severe irAEs frequently occur at gastrointestinal, pulmonary and dermatological organs, which show considerable expression of PD-L1 and PD-L2 (programmed death ligand 2) in healthy condition 6 , 7 , 8 . However, patients who experienced irAEs show a better prognosis 6 , 7 , 8 .…”

“…Severe irAEs frequently occur at gastrointestinal, pulmonary and dermatological organs, which show considerable expression of PD-L1 and PD-L2 (programmed death ligand 2) in healthy condition 6 , 7 , 8 . However, patients who experienced irAEs show a better prognosis 6 , 7 , 8 . It suggests that PD-1/PD-L1 based immune checkpoint blockade not only evoke anti-tumor immunity but also destroy the immune homeostasis in certain organs especially organs showing high expression of PD-L1 or PD-L2 9 , 10 .…”

Expert consensus on perioperative treatment for non-small cell lung cancer

“…It is advised to adhere to the important principle of “prevention, assessment, inspection, treatment, and monitoring” for the management of ICIs to ensure early and accurate detection, diagnosis, and treatment of irAEs ( 31 ). Evaluation and routine screening of NSCLC patients before initiation of immunotherapy may be the most important component of irAE management because it allows the patients likely to be most susceptible to irAEs to be identified and flagged for early intervention ( 32 ).…”