Baseline peripheral blood absolute lymphocyte count and survival outcomes in patients with PD-L1-positive advanced gastric cancer treated with immune checkpoint inhibitor plus chemotherapy.

Abstract

e16075 Background: Tumor PD-L1 expression guides the use of immune checkpoint inhibitor (ICI) plus chemotherapy in advanced gastric cancer (AGC), yet clinical benefit varies even among PD-L1–high tumors. Baseline peripheral blood absolute lymphocyte count (ALC), a marker of host immune competence, may influence the clinical impact of PD-L1 expression, but this has not been evaluated. We investigated whether baseline ALC influences the association between tumor PD-L1 expression and outcomes with first-line ICI plus chemotherapy. Methods: Using multicenter retrospective data (Asan Medical Center and Seoul St. Mary’s Hospital), patients treated with first-line ICI plus chemotherapy or chemotherapy alone were analyzed. PD-L1 was assessed by combined positive score (CPS; cutoffs 5 and 10). Baseline ALC was dichotomized at 1,880 cells/µL (maximally selected rank statistics). Progression-free survival (PFS) and overall survival (OS) were evaluated in PD-L1–ALC strata. Treatment benefit was assessed within strata, and multivariable Cox models included an interaction term. Results: Among 645 patients treated with ICI plus chemotherapy (n = 417 derivation; n = 228 validation), survival outcomes varied by PD-L1 and baseline ALC. Across CPS ≥5 and ≥10 in both cohorts, ICI plus chemotherapy showed the most favorable survival when both tumor PD-L1 expression and ALC were high. In contrast, when ALC was low, outcomes were poor even in the presence of high tumor PD-L1 expression and were comparable to those observed in PD-L1–low tumors. At CPS ≥10, median PFS was longest in the PD-L1–high/ALC–high subgroup (median PFS, not reached), followed by PD-L1–low tumors (9.1 mos), whereas PD-L1–high/ALC–low had similarly short PFS (8.0 mos). Similar patterns were seen for OS. The benefit was greatest in patients with CPS ≥10 and high ALC (PFS HR 0.31; OS HR 0.48), whereas attenuated benefit was observed in PD-L1–high patients with low ALC and in PD-L1–low subgroups. In multivariable models, ALC significantly modified the effect of ICI plus chemotherapy on PFS, with a stronger interaction in higher tumor PD-L1 expression (CPS ≥5: interaction HR 0.59, 95% CI 0.37–0.94, p = 0.025; CPS ≥10: interaction HR 0.40, 95% CI 0.21–0.75, p = 0.004). Conclusions: Baseline ALC dictated the clinical impact of tumor PD-L1 expression in AGC treated with first-line ICI plus chemotherapy. Favorable outcomes and the greatest relative benefit from adding ICI to chemotherapy were concentrated in patients with concomitantly high PD-L1 expression and high baseline ALC, whereas PD-L1–high patients with low baseline ALC experienced outcomes comparable to PD-L1–low disease. These findings suggest that baseline ALC may complement PD-L1–based clinical decision-making when guiding first-line ICI-based chemotherapy.