Key Considerations when Evaluating Whether to Establish a PD-L1 Laboratory Developed Test (LDT)

Abstract

Abstract Introduction/Objective Programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) testing is often used to identify patients with cancer who may be eligible for immune checkpoint inhibitor therapy. The complexity around using different assays and platforms has caused confusion and reluctance to perform in-house PD-L1 testing. Some labs have established a laboratory developed test (LDT) that may be used across multiple types of tumors. To evaluate the role of PD-L1 LDTs, ASCP formed an ad-hoc working group to identify key considerations. Methods/Case Report In early 2023, 40 pathologists and laboratory professionals joined the ASCP PD-L1 Learning Collaborative to explore ways to improve PD-L1 testing processes. An ad-hoc working group focused on LDTs and reviewed the literature, spoke with labs using LDTs, and developed guidance questions. Results (if a Case Study enter NA) The working group identified these key topics and questions: Testing volume and types of cancers: How many tests are performed each month to justify an in-house PD-L1 test? Which types of cancers are tested? Do we have (or do we plan to develop) reflex PD-L1 testing protocols for certain types of tumors? Buy-in from oncologists: Do our medical oncologists feel that a PD-L1 LDT provides the results they need to make treatment decisions across different types of cancers? Assay selection and testing platforms: Which IHC platform (eg, Ventana, Dako, Leica, etc.) do we currently use and which assay (eg, 22C3, 28-8, SP263, E1L3N, etc.) should we use? How well do these assays stain tumor cells vs. immune cells? IHC testing processes: What is our volume of IHC testing and how would adding PD-L1 impact our workflow for all IHC tests? How often do we encounter technical issues? How much staff time will it take to add PD-L1? What are the maintenance costs? Interpretation and scoring: Which pathologists are trained to interpret PD-L1 tests? Are they trained to interpret tumor cells, immune cells, or both? Do we train residents? Which scoring systems will we use and how will we report results? Validation: How many cases are needed for validation? Should validation samples include tumor cell and immune cell staining? Reimbursement: How will the lab be reimbursed for performing PD-L1 testing and interpretation? Conclusion Before establishing a PD-L1 LDT, the medical laboratory must review these questions against the backdrop of an evolving PD-L1 testing landscape. An LDT may be an appropriate approach for labs that aim to simplify PD-L1 testing based on the IHC platform(s) they are using.