Alessandro Di Federico: Intrapatient variation in PD-L1 and TMB

Alessandro Di Federico, Medical Oncologist and PhD student at University of Bologna, shared a post on X:

“Just published in Annals of Oncology our study investigating intrapatient variation in PD-L1 and TMB and the impact on outcomes to immunotherapy in patients with NSCLC.

Among 402 PD-L1 sample pairs and 413 TMB sample pairs, we found moderate concordance between PD-L1 paired assessments (ρ=0.53) and high concordance between TMB paired assessments (ρ=0.80). The time elapsed between assessments influenced PD-L1 concordance, but not that of TMB.

Regarding PD-L1, major increases (ΔTPS≥+50%) and decreases (ΔTPS≤-50%) were observed in 9.7% and 8.0% of cases, respectively. Copy number losses of CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2, located on chromosome 9p24, were found associated with PD-L1 major decrease (q<0.05).

Intervening ICI therapy between assessments was associated with a decrease in PD-L1. No other treatment was associated with PD-L1 variation. No intervening treatment was found associated with variation in TMB.

Variations in PD-L1 and TMB influenced outcomes to a subsequent ICI therapy. Among patients with multiple PD-L1 assessments before ICI, cases where all samples had a PD-L1 ≥1%, compared to cases with at least one sample with PD-L1 <1% and another with PD-L1 ≥1%, had high ORR and longer PFS.

In addition, in patients with at least one PD-L1 <1% and one ≥1% before ICI, cases where the most proximal sample was PD-L1 ≥1% had longer PFS compared to cases where the most proximal PD-L1 was <1%.

Regarding TMB, in patients with multiple TMB assessments before ICI, patients with TMB ≥10 mut/Mb based on the most recent assessment, as compared to those with TMB <10 mut/Mb, had high PFS and OS; instead, no differences were observed when patients were categorized using the oldest TMB assessment.

Main take-home message: retesting might be important. When feasible, in case of old PD-L1 and/or TMB assessments, retesting these 2 biomarkers should be considered before the start of a ICI therapy. Read the paper for many more analyses and details.”

Source: Alessandro Di Federico/X