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

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. Keywords: immunotherapy, elderly, PD-1 inhibitor, PD-L1 inhibitor, PDL-1 inhibitor, safety, immune-related adverse events, solid tumours, prognostic biomarkers