Nivolumab for patients with ND FL: Results from the phase II 1st FLOR study

Outcomes in patients with FL are influenced by host immune activity. Emerging evidence supports that combining CD20-directed therapy with PD-1i improves T-cell-mediated tumor cytotoxicity and NK cell antibody-dependent cytotoxicity, with additional data suggesting that immune priming with PD-1i before cancer-directed treatment may further improve therapeutic outcomes. The phase II 1st FLOR trial (NCT03245021) investigated nivolumab (a PD-1i) priming followed by nivolumab plus rituximab (an anti-CD20 mAb) in ND FL. 

A total of 39 patients with advanced-stage ND FL received nivolumab priming (240 mg IV every 2 weeks for 4 cycles), followed by nivolumab + rituximab (375 mg/m² IV every 2 weeks for 4 cycles), and maintenance with monthly nivolumab and 2-monthly rituximab. The primary endpoint was toxicity during induction. Efficacy outcomes included ORR, PFS, and OS.¹ Findings were published in Blood Adv by Barraclough et al.¹

Key learnings

The study met its primary endpoint, with 33% Grade ≥3 AEs occurring during induction; the most common were elevated amylase/lipase (15%), liver enzyme derangement (11%), and infection (10%). Overall Grade ≥3 AEs occurred in 59% of patients.

Serious AEs occurred in 46% of patients; the most frequent were infections (15%), fever, and pancreatitis (5% each). Nivolumab was discontinued due to toxicity in three patients; no treatment-related deaths occurred.

The ORR was 92%, with a CR rate of 59%. Median PFS was 61 months; 4-year PFS and OS were 58% and 95%, respectively. High intratumoral CD8A gene expression correlated with CR and prolonged PFS (p = 0.03).

Results from the 1st FLOR trial show that nivolumab priming followed by nivolumab + rituximab demonstrated durable responses and favorable safety in patients with ND FL. CD8A gene expression may help identify patients likely to benefit from this non-chemotherapy approach.