Real-World Efficacy and Safety of Off-Label Use of Immune Checkpoint Inhibitors (ICI) in Cancer: A Retrospective Cohort Study in Qatar

Introduction: Immunotherapy has been an attractive choice for cancer treatment based on an increased understanding of T cell biology and tumor immunology (1). The occurrence of Off-label prescribing in Oncology is higher than other disciplinaries for many reasons, such as difficulty to conduct studies, cancer have variety of types and stages, protocol combinations and lines of treatment (2-3). Off-label use of Immune Checkpoint Inhibitors (ICI) has been inevitable since their first FDA approval a decade ago. The evaluation of efficacy and safety of ICI in off-label indications is lacking. In this study, we will address this gap in literature. Objective: Evaluate the implications of off-label use of ICIs in terms of efficacy and safety in real-world practice. Primary objective is to evaluate efficacy: Complete response (CR), Partial response (PR), Progression disease (PD), Stable disease (SD), and safety: number of immune-related adverse events (irAEs) (Quantitative) and severity of irAEs (Qualitative). Methods: Retrospective cohort study. Our population included all adult patients who received one or more of the ICIs (Atezolizumab, Avelumab, Durvalumab, Ipilimumab, Nivolumab, Pembrolizumab) without an approved indication between 01/01/2017 and 30/06/2021. Data were collected through electronic medical records, pooled in data collection sheet, and analyzed using SPSS. Results: Over the study period, 836 cycles of ICI were evaluated for 103 patients. The most frequent identified indications were colorectal cancer (12.6%), hepatocellular carcinoma (12.6%) and breast cancer (11.7%). Pembrolizumab was the most prescribed ICI with (47.6%). Clinical response reported as 4 patients CR (3.88%), 14 patients PR (13.59%), 13 patients SD (12.62%); 57 patients progressed (55.33%). Safety data showed that 35 patients experienced 38 irAEs, of which 19 patients (48.7%) were treated with Nivolumab. Severity of irAEs were as follows; 19 severe (50%), 17 moderate (44.74%), 2 mild (5.26%). The most common irAEs were hepatic toxicities (23.68%), thyroid toxicities (15.78%) and hematological toxicities (10.53%). Conclusion: ICI might be efficacious in more indications yet to be approved in cancer management. However, the use of ICI out of the approved indications might not be as safe considering increased potential of irAEs. Further studies on extended use of ICI are needed.