Update on the prognostic value of a novel immune-related toxicity grading system (OST score) in patients with advanced solid tumours treated with immune checkpoint inhibitors (ICI).
Authors: Matthaios Kapiris, Aida Santaolalla, Sosipatros Bratsos, Sundeep Guhnam, Louisa McDonald, Mary Fitzpatrick-Greening, Moe Muhith, Yin Wu, Alexandros Georgiou, Debra Hannah Josephs, Debashis Sarker, Andrew Cope
Journal: Journal of Clinical Oncology (2024)

e14696 Background: Toxicity grading systems have been an asset in managing cancer patients undergoing systemic treatment. In the era of ICI treatment, correlation between toxicity and treatment response is becoming more apparent. A new toxicity score was developed with the aim of better defining the profile of immune-related toxicities (irAEs). Initial analyses also demonstrated its potential in predicting patient outcomes. Here we provide an update on the survival analyses. Methods: Data were collected from the Pathobiology of Adverse Immune Reactions (PAIR) prospective cohort study at Guy’s Hospital from February 2018 until December 2023. Patients with advanced solid tumours naïve to ICI who received at least 1 dose were included. Minimum 6 months of follow-up was required. IrAEs were captured based on the OST score which evaluates the number of affected Organs (O), number of Severe (S) CTCAE (≥G3) toxicities, and Total sum of all grade toxicities (T). OST was calculated as a cumulative score at the end of follow-up or death. Patients were divided in high and low toxicity groups, defined by the median value for each parameter. For the composite OST score analysis, patients were divided in 2 groups based on a point system; 1 point was attributed for each individual OST high parameter; high toxicity OST group included patients with score &gt;1. Descriptive statistics and crude and multivariate survival Cox Proportional Hazards regression analyses were performed accounting for age, tumour type, treatment, and steroid exposure. Results: A total of 148 patients fulfilled the criteria. Median age was 68 years (range 23-87), the majority were white Caucasian (81.8%) and male (56%). Melanoma was the most common tumour type (32.4%) followed by NSCLC (21.6%) and RCC (19.2%). 37.8% of patients received Ipilimumab/Nivolumab, 30.4% Pembrolizumab and 31.8% received other PD(L)-1 monotherapies. Twenty-eight patients (18.9%) had an autoimmune disorder at baseline; hypothyroidism was most common (5.4%). At end of follow-up, 82 deaths (55.4%) had occurred. Across the three OST parameters, Organ (O) was the strongest predictor of survival [HR (95%CI) 0.480 (0.265-0.869)]. After adjustment, multivariate analysis showed that risk of death was significantly lower in the high vs low Organ and Total toxicity groups [HR (95%CI) 0.379 (0.216-0.663) and 0.544 (0.302-0.982) respectively], but not for Severity [0.664 (0.338-1.306)]. In the OST combined score, the high toxicity group had favourable prognosis compared to low groups (mOS 56.6 vs 13 months) [HR (95%CI) 0.439 (0.275-0.702)]. Conclusions: Our new score manages to efficiently capture immune-mediated toxicity profile of patients treated with ICI as well as predict their outcomes. Further prospective evaluation, integration of laboratory markers and external validation is currently ongoing.