No, this tumor is PD-L1 negative.
A tumor proportion score (TPS) of <1% by the 22C3 pharmDx assay is classified as PD-L1 negative 1. This classification has direct therapeutic implications for treatment selection in non-small cell lung cancer.
PD-L1 Classification Using 22C3 pharmDx
The 22C3 pharmDx assay, which is the FDA-approved companion diagnostic for pembrolizumab, uses the following standardized cutoff values 1:
- TPS <1%: PD-L1 negative
- TPS 1-49%: PD-L1 positive (intermediate expression)
- TPS ≥50%: High PD-L1 expression
Your result of TPS <1% falls into the negative category by definition.
Clinical Implications for Treatment
For patients with PD-L1 negative (TPS <1%) adenocarcinoma, pembrolizumab monotherapy is not indicated 1. The FDA approval for pembrolizumab monotherapy requires either TPS ≥1% for second-line treatment or TPS ≥50% for first-line treatment 1.
However, this does NOT mean immunotherapy is completely off the table. For PD-L1 negative patients, the 2024 ASCO guidelines recommend 2:
- Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) - preferred combination
- Cemiplimab + carboplatin + paclitaxel - alternative combination
- Nivolumab + ipilimumab (with or without 2 cycles of platinum-based chemotherapy)
- Durvalumab + tremelimumab + platinum-based chemotherapy
The KEYNOTE-189 trial demonstrated that pembrolizumab combined with platinum-pemetrexed chemotherapy improved outcomes even in PD-L1 negative patients, with median OS of 17.2 months (HR 0.55) compared to chemotherapy alone 2.
Important Caveats
Pleural fluid specimens can be challenging for PD-L1 assessment 3. The cytology specimen may have:
- Background staining issues
- Difficulty distinguishing tumor cells from mesothelial cells and immune cells
- Sample fixation variability
If treatment decisions hinge critically on PD-L1 status, consider requesting PD-L1 testing on a tissue biopsy specimen if available, as concordance between pleural fluid cytology and tissue histology ranges from 78-82% 3, 4. Recent studies suggest PD-L1/TTF-1 dual staining improves accuracy in pleural effusion specimens, achieving 82% concordance with tissue 4.
Some patients classified as PD-L1 negative still derive clinical benefit from immunotherapy, particularly when combined with chemotherapy 1. The negative predictive value is not absolute, which is why combination regimens remain standard of care regardless of PD-L1 status.