Immuno-oncology (IO) drugs have demonstrated unprecedented benefits in the treatment of several types of cancer. The overall survival time of cancer patients treated by IO drugs have been dramatically extended, and in some cases, even late stage fatal cancers are brought into remission by the IO-based immunotherapy.
IO drugs work in a very unique way. Unlike the chemotherapy or targeted therapy drugs, IO drugs don’t target and kill cancer cells directly. Instead, they interact with the T-cells in patient’s immune system to help release more cancer-fighting power. For example, the most widely used IO drugs Nivolumab and pembrolizumab are PD-1 Immune Checkpoint Inhibitors (ICIs). Their function is to unlock the power of T-cells, the “soldiers” of the immune system, by taking off the “brake” function of immune “checkpoint” formed by the PD-1 molecules that prevent T-cells from attacking the cancer cells in patients.
IO drugs are actually effective for all types of cancer as the drugs target patients’ immune system, which is unrelated to the types of cancer patients have. This uniqueness allows ICIs to be used to treat many types of late stage cancers, including metastatic skin cancer (melanoma) and the cancers in lung, breast, bladder, kidney and head and neck. None of the conventional therapies, such as chemotherapy and radiation therapy, have showed such level of dramatic therapeutic outcomes before.
However, ICIs drugs are not perfect: they don’t work for everyone. The overall response rates to ICIs are only 15-20%, which means the majority of the patients won’t be able to get their therapeutic benefits. Information about which patients might benefit from which drugs is critical for doctors, but no conclusive data is available so far.
By analyzing results from multiple separate retrospective studies, researchers at different institutions found out that Tumor Mutational Burden (TMB) might be a useful biomarker for doctors to predict whether a patient would respond to and get the benefits of ICIs treatment. TMB is one of the data obtained from a genetic testing Whole-Exome Sequencing that measures the total number of disease-relevant gene mutations within a particular region of DNA in patients with solid tumors.
A high TMB Score indicates that the patient’s cancer cells might have enough targets for the T-cells to destroy them. This gives the doctors a practical clinical tool to identify the patients who are more likely to get the benefits from the ICIs treatment.
Tip to Patients #1: ask your doctor if you are eligible to have the TMB test. If you have already done the test, ask if your TMB score is high enough to receive the ICIs treatment.
The TMB-based assessment has been very helpful for doctors to make treatment decisions, but the final TMB score will be influenced by a variety of factors, such as sample quality and quantity, method of data analysis and the format of reporting. Standardization of testing and reporting procedures is the key to obtain a correct TMB score that enables doctors to make the right treatment decision. But doctors working at different hospitals may receive the TMB test results from different laboratories with different reporting formats, which make it very difficult for them to compare the results and make the right assessment before prescribing the drugs.
Tip to Patients #2: ask if your test was done by the Whole-Exome Sequencing (WES) method, which is the gold standard for TMB testing. If your TMB data was from other methods, such as the targeted sequencing panel, you may ask if the WES test could be conducted so that the data can be compared with each other.
Late stage cancers are much more complex than early stage ones as more gene alterations have happened during the course of disease. When making the decision on whether a patient should receive ICIs treatment, genetic testing results other than the TMB data, if available, should be considered together. This type of combined data analysis requires a high level of expertise, it is usually done by a multidisciplinary team called Molecular Tumor Board (MTB), where doctors and scientists from diverse specialty areas meet to find out the best treatment strategy for patients.
Tip to Patients #3: ask if your TMB data and all other genetic biomarkers could be analyzed and discussed by the Molecular Tumor Board (MTB). This is crucial as everything important for your cancer will be considered all together before the treatment decision is made.
New drugs bring new hopes to cancer patients—but only if the right drugs are used in the right way. We hope the information and tips provided in this short article help you or your loved ones to receive better treatment outcomes.
Additional Reads You May Enjoy:
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New Discovery May Significantly Broaden the Applicability of T-Cell Immunotherapy
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Karen Slattery saysJune 30, 2021 at 2:50 pm
I am not sure if my husband would be a candidate, but would like to meet with someone as soon as possible. Please let me know how to get in touch with someone in this area or near by that we could talk with or meet with. My husband has pancreatic/liver cancer and is his prognosis is not good. 513-741-0848 Karen Slattery
Ravi Chander saysAugust 3, 2022 at 1:57 am
Thank you for sharing the great article about the Immuno-Oncology Drug Treatment in three tips!
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