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A unique, late-breaking session at the 70th AACC Annual Scientific Meeting & Clinical Lab Expo in Chicago will give attendees the inside story on the development of one of the most notable diagnostic advances of the past decade, the programmed cell death 1 ligand (PD-L1) immunohistochemistry (IHC) test to determine which patients with non-small cell lung cancer are likely to benefit from pembrolizumab (Keytruda). This session also will explore novel tests for fibrillary glomerulonephritis (FGN) and light chain amyloidosis. The session speakers hope that together these presentations will inspire clinical laboratory professionals to blaze their own trails in advancing precision medicine.

Scientific session (34120) Precision Medicine: From Novel Biomarkers to Blockbuster Drugs takes place on August 1 from 10:30 a.m. to noon and is worth 1.5 CE hours. “Precision medicine is anchored in the hypothesis that molecular characterization of a disease (like cancer) will yield better outcomes for a patient,” session co-presenter Surendra Dasari, PhD, an assistant professor at Mayo Clinic in Rochester, Minnesota, told CLN Stat.

Plenty of evidence supports this hypothesis, Dasari said. “An effective way to advance precision medicine is to find high-quality biomarkers and translate them to the clinic. For example, translation of biomarkers that can predict drug response—companion diagnostics—is critical for matching the right patient to the right drug in oncology. This not only save lives by improving treatment efficacy but also reduces overall treatment costs.” Examples of great companion diagnostics already exist, such as the PD-L1IHC test for pembrolizumab (Keytruda). In the meantime, even more targeted therapies with new drugs are maturing through clinical trials, Dasari said.

Dasari will join Kenneth Emancipator, MD, DABP, executive medical director and head of companion diagnostics for Merck & Co., who led the team that developed the PD-L1 companion diagnostic for pembrolizumab. PD-L1 testing helps identify which patients are most likely to respond to anti-PD-1/PD-L1 checkpoint inhibitor therapy. As CLN reported in May, the Food and Drug Administration (FDA) has approved four (IHC)-based PD-L1 assays, one of which is the companion diagnostic Emancipator developed. This test allowed Keytruda to become the first immunotherapy to be approved for first-line treatment of non-small cell lung cancer. For this work, Emancipator and his colleagues received the 2015 PhRMA Research and Hope Award for Biopharmaceutical Industry Research on behalf of Merck.

Precision medicine is all about understanding the underlying biology of disease in individual patients, Emancipator told CLN Stat. Diseases that appear very similar clinically such as lung cancer may be very different biologically. Some lung cancers express PD-L1 while others do not. Some have epidermal growth factor receptor mutations or anaplastic lymphoma kinase gene rearrangements, others do not. “The only way we can identify these differences is to test the tumor biopsy for the relevant biomarker, which can then inform the optimal way to treat the cancer,” he said.

During his talk, Emancipator will detail what Merck and its diagnostic partners did to develop the PD-L1 companion diagnostic. “I’m going to describe how early clinical data influenced the development of the test, and then, conversely, how PD-L1 staining seemed to predict response to pembrolizumab. Finally, I will talk about the clinical trials that supported FDA approval of pembrolizumab for the treatment of non-small cell lung cancer along with the PD-L1 test as a companion diagnostic,” he said.

Attendees will see what a crucial role basic skills of laboratory science play in drug development in the age of precision medicine. “I think they will also see how important it is to incorporate precision medicine into their own laboratories—how important it is for patients to have access to relevant tests,” said Emancipator. “This is necessary, to get the right patient on the right drug at the right time, which is what precision medicine is all about.”

Principles of precision medicine are equally applicable to plenty of other diseases besides cancer. Dasari’s talk will focus on how to find biomarkers to address these unmet clinical needs. “More specifically, I will describe how we found a biomarker and pathogenic protein in FGN,” he said.

Although FGN was first described as a disease in 1977, the pathogenic protein involved in its development has never been found. “Hence, renal pathologists use a conglomeration of nonspecific histological, histochemical, and ultrastructural methods for diagnosing the disease. By finding the pathogenic protein, we not only imparted specificity to FGN diagnostic algorithms but also paved the way for developing targeted therapies that can eliminate the pathogenic protein,” Dasari said.

The second half of his talk will describe his team’s discovery of a serum-based biomarker that can predict whether a patient has light chain amyloidosis. “As of today, there is no specific biomarker for detecting amyloidosis in patients with monoclonal gammopathy,” said Dasari. “The current clinical methods rely on signs and symptoms of organ failure. Hence, these patients often get a late diagnosis leading to poor prognosis. Depending on the severity of organ failure, they end up needing a cardiac and/or renal transplantation. The new marker can help prevent this by enabling an earlier diagnosis for a subset of AL patients.”

Learn more about the technologies driving precision medicine at the 70th AACC Annual Scientific Meeting & Clinical Lab Expo July 29–August 2 in Chicago.