Development of a prognostic scoring system for patients with advanced cancer enrolled in immune checkpoint inhibitor phase 1 clinical trials

We sought to develop a prognostic scoring system to aid in patient selection for immune checkpoint inhibitor (ICI) phase 1 clinical trials. Clinical data from patients treated in phase 1 ICI clinical trials at MD Anderson (MDA) Center were analysed. Seventeen clinical factors were studied. Recursive partitioning analysis, a tree-based model, was used to develop a regression tree and identify optimal cut-points based on differences in survival for each clinical factor. A Cox proportional hazards regression model was then used to identify factors independently affecting overall survival. A prognostic scoring system was subsequently developed. A total of 172 patients (105 CTLA4- and 67 PD1-based) were analysed. Seven factors were independently associated with worse overall survival (OS): age>52 years (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.1–2.4), Eastern Cooperative Oncology Group performance status>1 (HR 2.81, 95%CI 1.3–6.3), lactate dehydrogenase >466 (which is 0.75 × the upper limit of normal at our institution) (HR 2.1, 95% CI 1.4–3.2), platelet count >300 × 10 3 μ L −1 (HR 1.8, 95% CI 1.2–2.8), absolute neutrophil count >4.9 × 10 3 μ L −1 (HR 2.3, 95% CI 1.5–3.5), absolute lymphocyte count <1.8 × 10 3 μ L −1 (HR 3.3, 95% CI 1.9–5.7), and liver metastases (HR 1.8, 95% CI 1.2–2.6). An index was created by dividing the cohort into risk groups based on the number of factors present: 0–2, 3, 4, or 5–6. Median OS was 24.2 months, 11.6 months, 8.0 months, and 3.8 months for patients with 0–2, 3, 4, or 5–6 risk factors, respectively; log-rank test, P <0.0001. The Harrell c-index of this scoring system was 0.72, indicating better predictability than the Royal Marsden Hospital score (c-index 0.67) and MDA score (c-index 0.61). We have developed a novel ‘MDA-ICI’ prognostic scoring system for patients treated in phase 1 ICI clinical trials. Prospective evaluation and external validation is warranted and may help aid patient selection for future clinical trials.