Validation of E1L3N antibody for PD-L1 detection and prediction of pembrolizumab response in non-small-cell lung cancer

Commun Med (Lond). 2022 Nov 1;2(1):137. doi: 10.1038/s43856-022-00206-4.

Abstract

Background: The programmed death-ligand 1 (PD-L1) 22C3 assay is one of the approved companion diagnostic assays for receiving anti-programmed cell death ligand 1 (PD-L1) therapy. Our study evaluated the performance of E1L3N and 22C3 antibodies in estimating PD-L1 expression in non-small cell lung cancer (NSCLC).

Methods: Our retrospective study included 46 patients diagnosed with unresectable EGFR/ALK/ROS1-negative NSCLC who received first-line pembrolizumab therapy between 2018 and 2021. PD-L1 immunohistochemistry of baseline tissue biopsy samples was performed using PDL1-E1L3N and PDL1-22C3 antibodies. The concordance between the PD-L1 assays and the treatment outcomes was assessed.

Results: Using a tumor proportion score (TPS) cutoff of ≥1%, 67.4% of patients are evaluated to be positive using PDL1-E1L3N and 73.9% using PDL1-22C3. Using a TPS of ≥50% as the cutoff, 26.1% of patients are positive using PDL1-E1L3N and 30.4% using PDL1-22C3. The PDL1-22C3 and PDL1-E1L3N assays are highly concordant and reveal a correlation coefficient of 0.925 (p < 0.0001). Patients with PDL1-E1L3N TPS > 50% have a significantly higher objective response rate than patients with PDL1-E1L3N TPS < 1% (p = 0.047), with a similar trend observed for PDL1-22C3 (p = 0.051). Consistent with PDL1-22C3, patients with higher PDL1-E1L3N expression (≥50%, 1-49%) have longer progression-free survival than those with PDL1-E1L3N TPS < 1%.

Conclusion: Our study provides clinical evidence on the concordance of PD-L1 TPS scores between clones E1L3N and 22C3. Moreover, the treatment responses to pembrolizumab are also comparable between the PDL1-E1L3N and PDL1-22C3. These findings indicate that E1L3N is a reliable and cost-effective assay and may serve as an alternative to 22C3.

Plain language summary

To determine which patients might be suitable to receive immunotherapy, a type of cancer treatment that triggers the immune system to target the patient’s tumor, a PD-L1 test is sometimes used. This test looks at the levels of PD-L1, which indicate whether immunotherapy might work in the patient. One of the tests commonly used can be expensive and a reliable and cost-effective alternative is needed. Here, we compare the results of PD-L1 testing with that test with an alternative that is more cost-effective. We show that the two tests are highly concordant, and also demonstrate that the results using the alternative test are able to predict response to immunotherapy in patients with advanced non-small cell lung cancer. Our findings provide evidence that the alternative, more cost-effective test might be useful and reliable in the clinic.