CELL INTELLIGENCE · 肿瘤细胞治疗研究

Follicular lymphoma (FL) outcomes are influenced by host immune activity. CD20-directed therapy plus programmed cell death 1 inhibition (PD-1i) increases T-cell tumor killing and natural killer cell antibody-dependent cell cytotoxicity. Mounting evidence supports immune priming using PD-1i before cancer directed agents. Our multicenter, phase 2 1st FLOR study enrolled 39 patients with previously untreated advanced-stage FL to receive 4 cycles of nivolumab (240 mg), then 4 cycles of 2-weekly nivolumab plus rituximab 375 mg/m2 (induction), then 1 year of monthly nivolumab (480 mg) plus 2 years of 2-monthly rituximab maintenance. Participants with complete response (CR) after nivolumab priming continued nivolumab monotherapy. The primary end point was toxicity during induction. Adverse events of grade ≥3 during induction occurred in 33% (n = 13); most commonly elevated amylase/lipase (15%), liver enzyme derangement (11%), and infection (10%). Three patients discontinued nivolumab secondary to toxicity. Overall response rate was 92% (CR, 59%). Median follow-up was 51 months. Median and 4-year progression-free survival (PFS) were 61 months (95% confidence interval [CI], 2-72) and 58% (95% CI, 34-97); 70% of responders remained in CR. The 4-year overall survival was 95%. High baseline total metabolic tumor volume (TMTV) and total lesion glycolysis conferred inferior PFS (P = .04 and P = .02). Additionally, high baseline tumor CD8A gene expression was associated with improved PFS (P = .03). Nivolumab priming followed by nivolumab-rituximab in treatment-naïve FL is associated with favorable toxicity and high response rates, potentially providing an alternative to chemotherapy. TMTV and high tumor CD8A expression are promising immunotherapy biomarkers for FL. This trial was registered at www.ClinicalTrials.gov as #NCT03245021.