Is There a Tumor Proportion Score Threshold at Which Tumor-Cell PD-L1 Adds Prognostic Information Beyond the International Prognostic Index in Large B-Cell Lymphoma?

Background/Objectives: In diffuse large B-cell lymphoma (DLBCL), the prognostic value of programmed death-ligand 1 (PD-L1) depends on the immunohistochemical threshold applied. We asked whether tumor-cell PD-L1 adds prognostic information beyond the International Prognostic Index (IPI). Methods: Tumor-cell PD-L1, quantified by the 22C3 tumor proportion score (TPS), was assessed retrospectively in 95 patients with large B-cell lymphoma (87 DLBCL-NOS) given frontline chemoimmunotherapy. TPS was analyzed at the prespecified ≥1% threshold, post hoc at ≥10%, ≥25%, ≥50% and ≥70%, continuously, and with restricted cubic splines. Results: PD-L1 positivity (TPS ≥ 1%) was present in 73 patients (77%). After a median follow-up of 89.8 months, PD-L1 was not independently associated with overall survival (OS; adjusted hazard ratio [HR], 0.73; 95% CI, 0.35-1.53) or progression-free survival (adjusted HR, 0.91; 95% CI, 0.44-1.86); no threshold survived correction for multiplicity. An unadjusted association with OS emerged at TPS ≥ 70% (HR, 2.02; 95% CI, 1.02-4.02), but these patients more often had an IPI ≥ 3 (72% versus 36%) and it was attenuated after adjustment (1.53; 0.74-3.18). No definition improved model fit or discrimination beyond the IPI; the null result held in DLBCL-NOS and R-CHOP subgroups. Conclusions: Tumor-cell PD-L1 did not add prognostic information beyond the IPI for overall survival.