Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram

• Published in: Frontiers in immunology Vol. 15; p. 1323151
• Main Authors: Losurdo, Agnese, Dipasquale, Angelo, Giordano, Laura, Persico, Pasquale, Lorenzi, Elena, Di Muzio, Antonio, Barigazzi, Chiara, Korolewicz, James, Mehan, Aman, Mohammed, Oreoluwa, Scheiner, Benhard, Pinato, David J, Santoro, Armando, Simonelli, Matteo
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: Carcinoma, Non-Small-Cell Lung - pathology; early-phases clinical trials; Humans; immune-related adverse events; Immunology; immunotherapy; Immunotherapy - adverse effects; Lung Neoplasms - pathology; next-generations immunotherapies; Nomograms; Patient Selection; Prognosis; prognostic scores; Retrospective Studies; Serum Albumin; early-phases clinical trials; prognostic scores; next-generations immunotherapies; immune-related adverse events; immunotherapy
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1323151

Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations. We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation. A total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36-0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram. Prior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent.