Precision medicine advances means more options for more diagnoses

By MELANIE KILGORE-HILL

Pharmacogenomics is a game changer in the field of precision medicine, and now patients and providers in Arkansas are reaping the life-changing benefits of the study between DNA and drug response.

More precision

“Precision medicine’s aim to deliver precise healthcare, and pharmacogenomics, which is really a study of both pharmacology and genomics, deals with the understanding of how drugs and genes are interrelated - so we can treat patients better,” explained clinical informatics specialist Feliciano “Pele” Yu, MD, a pediatrician and Chief Medical Information Officer at Arkansas Children’s Hospital and professor of Pediatrics, Biomedical Informatics and Public Health at the University of Arkansas for Medical Sciences (UAMS). Yu was instrumental in the launch of Arkansas Children’s pharmacogenomics program with his informatics expertise.

In 2018, the Pediatric Precision Medicine program was founded by Bradley Schaefer, MD, Professor of Genetics and Pediatrics at UAMS. The program was born from a generous philanthropic grant supporting precision medicine through the Arkansas Children’s Research Institute. Schaefer also runs a precision medicine consultation service at his Arkansas Children’s Northwest clinic.

Leveraging data

While oncology and hematology were among the earliest adaptors of precision medicine, Yu said the science is impacting every facet of healthcare including cardiology, gastroenterology, psychology and addiction medicine, among others.

“Caring for patients in pharmacogenomics requires a lot of information, and we’re challenged to combine these healthcare data points and crunch numbers to provide that information in a meaningful way to providers and their patients,” Yu said. “Biomedical informatics is concerned with using information technology and healthcare in improving patient care, and in Arkansas we’re really leveraging digitized genomic and clinical data for the future of medicine.”

In pharmacogenomics, a patient sample is run through a machine capable of detecting specific genetic abnormalities, or mutations that are associated with a drug’s metabolism.

“Research has known for years that a particular drug, when given to particular patient, could also have adverse effects or conditions that would make the drug ineffective,” Yu said. “Pharmacogenomics can be used to describe the potential serious side effects or provide additional information about the appropriate drug dosing that may be effective for patients. We’re very fortunate here in Arkansas to have this technology and want to make it available to all.”

Arkansas Children’s laboratory testing instrument currently detects 175 mutations that cover more than 50 genes and the technology to program a number of drug-gene interactions directly into the hospital’s clinical information systems.

“One of the fortunate things we have is a very robust electronic health record (EHR) capable of capturing information in a way that we can provide it back to prescribing physicians in a timely manner,” Yu said. “Arkansas Children’s Hospital is able to link those things in a meaningful way so physicians can get the best information possible.”

Left to Right: Feliciano Yu, Eric Schaefer, Sam Makhoul

Staying connected

Sam Makhoul, MD, medical director of clinical research at Little Rock-based CARTI, said EHR connectivity is key for continued growth of pharmacogenomics. An independent, not-for-profit cancer care provider, CARTI treats more than 35,000 patients each year from every county in Arkansas, and across the country.

“This science will take us a long distance if handled well,” Makhoul said of pharmacogenomics. “We must implement and maintain well connected EHRs and genomics platforms, both locally and nationally. As we learn more about the profile of disease and which patients are at high risk, that will guide us dramatically as we collect more data in the same platform.”

Makhoul also stressed importance of patients being allowed full participation in the process including access to their EHR, with the opportunity to provide feedback and patient reported outcomes.

“There’s a huge opportunity to remove the ceiling here and take this to the next level,” he said. “The best technology needs the best structure for each patient, because the patient is ultimately at the center of this.”

Makhoul said precision medicine has become standard of care for most metastatic cancer patients at CARTI, and is proving essential for patients with Lynch syndrome or to women with BRCA mutations as well.

“It’s important to know every breast cancer patient’s genetic profile,” Makhoul said.

Options in oncology

In Northwest Arkansas, Highlands Oncology Group has been among the region’s earliest adapters of precision medicine, with oncologists now working to promote the science in the broader healthcare community.

“We keep trying to educate non-oncologists that there are a lot of newer and more targeted approaches in how cancer is treated compared to our older classic chemotherapies,” said Eric Schaefer, MD.

Highlands Oncology has been heavily involved with clinical trials involving precision medicine since the 1990s, and their clinical trial program is nationally recognized and has been instrumental in Highlands’ continued growth. Schaefer said alternative therapies are particularly well received among older patients.

“The biggest benefit is that the newer therapies, such as immunotherapies, are much better tolerated and more effective than classic chemo,” he said of the older population. “Probably half of patients have seen immunotherapies advertised but don’t fully understand what they are, and many are relieved to be treated with a non-chemotherapy regimen.”

He encourages PCPs to refer even older, non-fit patients to medical oncologists to discuss available options. While not everyone is eligible for targeted therapies, oncologists often have options outside of traditional treatment. Schaefer is particularly optimistic about a new therapy called Theranostics, which is currently being used by Highlands Oncology for the treatment of prostate cancer.

“Prostate cancer cells have specific antigen on their surface which diagnostic radiotracers can bind to, allowing a special diagnostic PET scan to detect a minute focus of cancer,” Schaefer said. “We can either treat this focus with external beam radiation (if it is a solitary focus) or through an IV infusion - where the diagnostic radioisotope is replaced with LU-177, a radioligand that selectively targets and kills the cancer cells. It’s better tolerated and more effective than some older treatment methods.”

While outcomes depend on mutation and disease type, Schaefer said immunotherapies are now available for 37 cancer types. He’s especially hopeful for the future of lung cancer treatment, since Northwest Arkansas is home to the largest lung cancer screening program in the nation thanks to Highlands’ free low dose CT scans. Between 60 to 100 eligible patients are screened through the program each week, resulting in findings of stage I lung cancer in 1 in 63 patients.

“This has become a hugely successful program in Arkansas, and we’re proud to be able to offer it at no cost,” Schaefer said.

Looking forward

Yu continues to work with providers to help them understand constraints and abilities of pharmacogenomics. Common concerns include patient costs, the consent process, training, turnaround time and sharing test results with patients. Funding of lab equipment and specialty pharmacists also pose constraints for smaller hospitals. To that end, Yu has helped establish a pharmacogenomics consultation service at Arkansas Children’s, continues to write papers and book chapters for regional and national publications, and takes on speaking engagements.

“We want providers to know it’s available, and which gene-medication pairing offers the best evidence,” he said.

He’s also spreading awareness about the nuances of pharmacogenomics between pediatric and adult populations.

“Most genes express early, but some express later as a child develops, depending on the child’s physiology,” he explained. “Sometimes gene expression is associated with patient level of development, so we have to make sure we’re testing at the appropriate age and growth stage. When you’re able to detect things early you have an advantage, not only for treatment but also prevention. Our goal and the most exciting part of this is the ability to predict what could happen and make necessary adjustments in care. The future of medicine here in Arkansas is precision health, and that includes preventative and predictive opportunities. Pharmacogenomics sits in the middle and gives us a more extensive and personalized approach to health care.”

Additional Resources

• ACH link to Pharmacogenomics Service- https://www.archildrenspho.org/programs-and-services/precision-medicine?journey=symptoms&accordion=accsection-E52B6B23FCE440CF946FEEAA768FDBAB
• Paper for Arkansas Childrens Pharmacogenomics experience - https://pubmed.ncbi.nlm.nih.gov/34064668/

Gill PS, Yu FB, Porter-Gill PA, Boyanton BL, Allen JC, Farrar JE, Veerapandiyan A, Prodhan P, Bielamowicz KJ, Sellars E, Burrow A, Kennedy JL, Clothier JL, Becton DL, Rule D, Schaefer GB. Implementing Pharmacogenomics Testing: Single Center Experience at Arkansas Children's Hospital. J Pers Med. 2021 May 11;11(5):394.

• Local Healthcare Journal of Arkansas article - https://www.healthcarejournalar.com/sites/default/files/journal/fb/HJAR-2021-jul-aug/33/

Porter-Gill PA, Gill PS, Yu FB, Schaefer GB. Precision Medicine in Arkansas. Healthcare Journal of Arkansas. 2021, July/August:32-33.

• Local The journal of the Arkansas Medical Society - https://viewer.joomag.com/med-journal-august-2021/0831836001627394260?short&

Porter-Gill PA, Gill PS, Schaefer GB, Allen JC, Boyanton BL, Yu FB. Arkansas Physicians’ Interests and Learning Opportunities with Pharmacogenomics. The Journal of the Arkansas Medical Society. 2021, August; 118 (2): 30-32.