The Rechallenge Benefit Score: A Clinical Decision Tool for Patients Progressing After Immunotherapy
Résumé
Background: Most patients with advanced Non-Small-Cell Lung Cancer (NSCLC) receive an immune checkpoint inhibitor (ICI) as a first-line treatment. Therapeutic options upon progression are limited, making ICI rechallenge a potential strategy. However, identifying patients who may benefit from this approach remains a challenge. This study presents a predictive score based on routine blood tests to identify patients who can specifically respond to rechallenge. Methods: We retrospectively collected data from 252 advanced NSCLC patients who received first-line ICI between 2015 and 2021 across 16 French Oncologic Centers. Patients had received ICI rechallenge (Rechallenge cohort; N = 80) or chemotherapy (Chemotherapy cohort; N = 82) after progression. Results from 17 routine blood tests conducted before the first and second cycles of treatment were collected. Relevant blood tests associated with progression-free survival over rechallenge (rPFS) were identified using Cox regression and validated through a Bootstrap Cox-LASSO machine learning approach. An integrative score was then developed and tested for its ability to stratify patients on rPFS. Results: Patients in the Rechallenge cohort showed a better ECOG PS and a deeper clinical benefit over the first ICI, compared to the Chemotherapy cohort. However, rPFS and PFS over the first chemotherapy post-ICI were similar (3.0 vs. 3.1 months, p = 0.4) justifying the identification of biomarkers for the decision-making. We defined the Rechallenge Benefit Score (RBS) able to identify patients likely to achieve longer clinical benefits from ICI rechallenge (C-index 0.79) regardless of their clinical features. The RBS was computed from routine blood-tests including inflammation-based markers such as the dNLR (derived Neutrophils to Lymphocytes ratio) and the MLR (Monocytes to Lymphocytes Ratio), but also AST (Aspartate Transferase), ALP (Alkaline Phosphatase), and Albumin. The median rPFS was 6.4 months for patients with a low RBS versus 1.9 months for those with a high RBS (p < 0.0001, HR = 0.31 (CI 0.17 – 0.55)). Interestingly, no difference in PFS was observed between patients with high versus low RBS in the chemotherapy group or in the first ICI cohort. Conclusion: We presented and validated the RBS score able to identify patients who respond to ICI rechallenge using routine blood tests. Since clinical features alone are inadequate for selecting patients, our findings can help in formulating treatment strategies for patients who already received immunotherapy during their history of disease.
| Origine | Fichiers produits par l'(les) auteur(s) |
|---|
