Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Methods: Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Results: Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001). Conclusion: Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.

Postinfusion PD-1+ CD8+ CAR T cells identify patients responsive to CD19 CAR T-cell therapy in non-Hodgkin lymphoma.

ABSTRACT: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Robust biomarkers and a complete understanding of CAR T-cell function in the postinfusion phase remain limited. Here, we used a 37-color spectral flow cytometry panel to perform high dimensional single-cell analysis of postinfusion samples in 26 patients treated with CD28 costimulatory domain containing commercial CAR T cells for NHL and focused on computationally gated CD8+ CAR T cells. We found that the presence of postinfusion Programmed cell death protein 1 (PD-1)+ CD8+ CAR T cells at the day 14 time point highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR T cells, including PD-1+ T cell factor 1 (TCF1)+ stem-like CAR T cells and PD-1+ T-cell immunoglobulin and mucin-domain containing-3 (TIM3)+ effector-like CAR T cells that correlated with improved clinical outcomes such as response and progression-free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here, we identified robust biomarkers of response to CD28 CAR T cells and highlight the importance of PD-1 positivity in CD8+ CAR T cells after infusion in achieving CR.