Abstract P070

Kinetics of PD-1 Blockade on Circulating CD8+ve T Cells After Exposure to low-dose Nivolumab

Introduction: Low-dose (40 mg) nivolumab results in near-complete saturation of PD-1 receptors on circulating T cells, suggesting that current dosing schedules may exceed the biological requirements for effective target engagement in classical Hodgkin lymphoma (cHL). Here we evaluate the durability of PD-1 receptor occupancy (RO) following treatment cessation in patients enrolled in an ongoing trial of low-dose nivolumab in advanced-stage cHL.

Methods: Peripheral blood samples were collected at baseline, immediately following nivolumab infusion, and at 2-week intervals following the final nivolumab dose up to 12 weeks. PD-1 RO on circulating T cells was assessed using a standardized flow cytometry-based assay.

Results: Between August 2024 and January 2026, 44 patients were enrolled onto the nivolumab arm, of whom 34 completed all four planned doses and had at least one follow-up sample available for analysis. At baseline, the PD-1 expression on circulating CD8+ T cells was 44.2% (range 10.5–85.8%). One hour after nivolumab infusion, median PD-1 RO was 99.7% (IQR 97.3–99.95%). Five patients (18.5%) demonstrated <90% RO including one patient with occupancy of only 44.3%. Following the final nivolumab dose, RO remained high at week 2, with a median occupancy of 99.8% (IQR 97.3–99.9%); however, 4/34 patients (11.8%) demonstrated RO <90%. At 12 weeks following the final infusion, median RO remained 99.9% (IQR 95.5–99.9%), with 4/28 evaluable patients (14.3%) demonstrating occupancy <90%. Thus, near-complete PD-1 RO was maintained in most patients for up to 12 weeks following the last dose of nivolumab.

Among 29 patients who completed 6 cycles of therapy, one had progressive disease at end-of-treatment and three relapsed within one year. No clear association was observed between RO and remission status. Three of four patients with subsequent progression or relapse maintained near-complete RO throughout the 12 week period of testing, while several patients with occupancy <90% remained in remission.

Conclusions: PD-1 RO remained near-complete for up to 12 weeks post-nivolumab, indicating prolonged target engagement after low-dose nivolumab. Current 2-weekly dosing intervals may therefore exceed the biological requirements for sustained target engagement. The lack of an apparent association between RO persistence and clinical outcome suggests that receptor saturation alone may be an insufficient biomarker of therapeutic efficacy.