Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, demonstrated longer median overall survival (7.5 vs 5.1 months) and improved response (13.3% vs 5.8%) versus investigator’s choice (IC) therapy in patients with recurrent SCCHN after platinum failure in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial. We screened peripheral blood lymphocytes (PBL) to identify biomarkers that may predict response to nivolumab.
Paired baseline (day 1) and on-treatment (day 43) PBL samples (n=36; 24 nivolumab; 12 IC) were analyzed using multicolor flow cytometry and a noncompeting anti-PD-1 antibody. Results were correlated with clinical outcome: responders (complete/partial response) and nonresponders (stable/progressive disease).
Levels of CD8+ T cells at baseline and on treatment were higher in nivolumab responders compared with nonresponders (23% vs 13%; P<0.05). PD-1+ CD8+ and PD-1+ CTLA-4+ CD8+ effector T cells (likely exhausted T cells) decreased ~2-fold following nivolumab in responders and nonresponders (P<0.05), whereas the decrease in CTLA-4+ CD8+ effector T cells following nivolumab was significant in responders only (8% vs 5%; P<0.05). PD-1+ TIM-3+ CD8+ effector cell levels decreased following nivolumab in nonresponders only (11% vs 7%; P<0.05); a similar nonsignificant reduction was observed in responders. PD-1+ Treg levels were lower in responders than nonresponders at baseline (19% vs 33%; P<0.01), and following nivolumab (12% vs 20%; P<0.001). As in T-effector cell populations, PD-1+ Tregs decreased ~1.6-fold after nivolumab in both responders and nonresponders (P<0.01). Baseline Ki67+ Treg levels were lower in nonresponders (28% vs 17%; P<0.05).
Response to nivolumab may be associated with higher levels of CD8+ T cells and CTLA-4+ CD8+ effector T cells, and lower PD-1+ CD8+ effector T cells and PD-1+ Tregs at baseline. Targeting both PD-1 and CTLA-4 axes is warranted in SCCHN to overcome suppressive signals in CD8+ effector T cells and in Treg cells expressing both checkpoint receptors.