PD-L1, PD1, TMB and Lung Cancer

Understanding the Roles of PD-L, PD1 and TMB in Lung Cancer Treatment

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

Researchers have identified certain biomarkers in lung cancer tumors. PD-L1 and TMB are biomarkers that may help provide information about whether or not a patient will benefit from immunotherapy to treat their lung cancer.

What are PD-L1 and PD-1?

Immunotherapy activates the immune system to attack cancer cells. The most common type of lung cancer immunotherapy is called an immune checkpoint inhibitor. Several immune checkpoint inhibitors for lung cancer block, or “inhibit” the interaction between PD-1 and PD-L1. PD-1 is a receptor often on the surface of immune cells. PD-L1 is a protein that has a broader presence, including on the tumor cells. High-levels of PD-L1 is one biomarker physicians look for in patients with lung cancer. Some immune checkpoint inhibitors target another type of immune protein called CTLA-4 and are used with PD-L1 inhibitors.

How do you know your levels of PD-L1 and what do they mean?

At the time of diagnosis, all new lung cancer patients should have their PD-L1 levels tested. This involves looking at tumor tissue under a microscope using a laboratory technique called immunohistochemical (IHC) staining. A PD-L1 test measures what percentage of cells in a tumor “express” PD-L1. Tumors that express high amounts of PD-L1 (50% or greater) may respond particularly well to checkpoint inhibitors.

If you have not had your PD-L1 levels tested, ask your doctor if it is right for you.

Learn more about the different types of biomarker tests.

How does PD-L1 level impact treatment options?

Results of PD-L1 tests help to inform treatment options. If you have high levels of PD-L1 and no other biomarker with an approved targeted therapy, then your doctor will likely recommend an immunotherapy drug as a first-line treatment. This means you get an immunotherapy drug before any other treatment. You may also receive chemotherapy at the same time.

Your doctor may recommend immunotherapy combined with chemotherapy if you have some expression of PD-L1, but less than 50%. Ask your doctor about your PD-L1 levels and what they mean for your treatment options.

What is TMB?

TMB stands for tumor mutation burden. Tumor mutation burden looks for the number of mutations in a tumor that can change proteins in a patient's tumor cells. For immunotherapies to work, the immune system must recognize one of these abnormal proteins. That is why it is thought that having more mutations may improve your chance of responding well to immunotherapy. Talk with your doctor about this test and if it is right for you.

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.