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

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

Introduction: 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. Patients and methods: 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. Results: 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. Conclusions: 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.

LONDON (England); PATIENT selection; NON-small-cell lung carcinoma; CLINICAL trials; NOMOGRAPHY (Mathematics); SERUM albumin

Frontiers in Immunology, 2024, p1

1664-3224

Academic Journal

10.3389/fimmu.2024.1323151