Table 1.
Scoring algorithms for the companion diagnostic assays of immuno-oncology (IO) agents.
| Anti–PD-1/PD-L1 Therapeutics | Atezolizumab | Avelumab | Durvalumab, Avelumab, and Tislelizumab | Nivolumab | Pembrolizumab |
|---|---|---|---|---|---|
| Assay | VENTANA PD-L1 (SP142) Assay [52] | PD-L1 IHC pharmDx 73-10 [not FDA approved] | VENTANA PD-L1 (SP263) Assay [53] | PD-L1 IHC pharmDx 28-8 [50] | PD-L1 IHC pharmDx 22C3 [51] |
| Scoring algorithm | IC ≥ 5%; number of PD-L1–positive tumor-infiltrating ICs as a proportion of the total TC and IC area | TC ≥ 5%; number of PD-L1–positive TCs as a proportion of the total TC area | TC or IC ≥ 25%; number of PD-L1–positive TCs with membrane staining as a proportion of the total TC area or PD-L1–positive ICs with membrane, cytoplasm, or punctate as a proportion of the total IC area. | TC ≥ 1%; number of PD-L1–positive TCs as a proportion of the total TC area | Number (Count) of PD-L1–positive TCs and number of PD-L1–positive ICs as a proportion of the total TC area |
| Typical staining characteristics | Dot-/ant-like staining pattern Low tumor cell staining Strong IC staining Developed for immune cell scoring |
Homogenous tumor cell staining Mostly strong staining intensity for TCs and ICs |
Homogenous tumor cell staining Moderate-strong staining intensity |
Homogenous tumor cell staining Mostly weak staining intensity |
|
| Design Considerations | Plasma cells have to be excluded from scoring All immune cells are included (incl. neutrophil granulocytes) |
Immune cell positivity is scored according to the area occupied by all immune cells (IC-“Area”-score) TC and IC are scored independently. Patients are positive when exceeding one of the two cutoffs or both PD-L1 can also be considered high if: ICP * > 1% and IC+ ≥ 25%; or, ICP * = 1% and IC+ = 100%. Plasma cells have to be excluded from scoring All immune cells are included (incl. neutrophil granulocytes) |
Combined positive score including immune cells and tumor cells Plasma cells have to be excluded from scoring Neutrophil granulocytes not included |
* ICP, tumor-associated immune cells in the tumor area.