Genomes: Technological advances offer challenges, opportunities

Genomic sequencing of cancer cells has led to the discovery of tumor-driving mutations and targets for therapy. But to seize the opportunities presented by genomic technologies, medicine must develop information “structures for robust, detailed meta-analyses of cohort studies, sharing sequence data, clinical parameters,” and data from different patient populations, said Ross L. Levine, MD, physician-scientist, Memorial Sloan Kettering Cancer Center, New York, Sunday, December 6 at the 57^th American Society of Hematology (ASH) Annual Meeting, held in Orlando.

Levine was a speaker at the ASH/European Hematology Association Joint Symposium, “Impact of Genomes: How Well Are We Incorporating the Assessments of Actionable Results.”

Dr. Levine“Precision medicine” is not truly a new concept, Levine said. “Physicians use patient-specific parameters to make decisions about patient care every day: Exam results, laboratory results, radiographic studies. And it has long been established that chromosomal alterations and cytogenetics can be used to risk-stratify patients with hematological malignancies and to guide the use of targeted therapies.”

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What’s new is the proliferation of genomic technologies, including next-generation gene sequencing, and the enormous amount of new data those technologies can, potentially, bring to bear on clinical decision making. That presents both “new challenges, and opportunities,” Levine said.

“Less-expensive, faster sequencing platforms are making sequencing accessible on a global scale,” he said, noting that sequencers are not available that are small enough to fit in the palm of a hand.

That technology is generating “an ever-expanding wealth of cancer genomic data,” such as that captured in The Cancer Genome Atlas Project (TCGA)-and not surprisingly, increasing use of genomics in the clinic, he noted.

“There is increasing data available from genomic studies of patients with hematologic diseases, and constant, rapid improvement in sequencing technology and analysis,” Levine said. “There’s been an expansion of clinical-grade genomic profiling platforms in academic and health care centers, and offered by central laboratories.”

Despite this boom in technological capacity, however, “most U.S. patients do not get genomic profiling as part of their routine clinical care,” he pointed out.

NEXT: Challenges to implementing genomic practice

Challenges to implementing genomic practice in the clinic include questions about the reliability and “robustness” of genomic data, and how it can be used to guide prognostication and treatment decisions, Levine said. Accessibility of genomic platforms in the clinic, regulatory and reimbursement issues, and clinician understanding of genomic data and platforms, are all important barriers to implementation of medical genomics in routine clinical care, he said.

“The problem is, the data are not always clear,” he said. Conflicting data on the prognostic value of a given mutation is common, frequently because biomarker and genomic studies often report findings based on relatively few patients.

Levine called on hematologists to “develop efforts to combine clinical, genomic, therapeutic response data from patients with hematologic diseases receiving clinical care on or off clinical trials,” citing the American Society of Clinical Oncology’s CancerLinQ real-time database as analogous efforts that have been undertaken “largely focused on solid tumors.”

“There is a critical need for similar studies in hematologic malignancies and disorders,” Levine said.

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ASH’s creation of a Task Force on Precision Medicine is an important first step toward that goal, he said.

But organizing the data and making it accessible is just part of the challenge, he was quick to note. Guidelines are needed to harmonize research conducted in different labs and different regions. And regulatory guidelines are needed, too, he said, citing “variability in state-to-state guidelines for genomic testing.”

“The role of the FDA in regulating genomic assays is evolving,” Levine said. “Assays linked to a specific lesion which directs to a targeted therapy, are carefully regulated. But there’s less clear guidance on regulation of prognostic assays and assays which guide the use of standard therapies like chemotherapy.”

Reimbursement is another important barrier to implementation of genomics in the clinic, he noted. “There are important questions regarding panel-based versus gene-based reimbursement” for testing, he noted.

“ASH and the hematology community need to be an active participant in setting standards and guidelines,” Levine said. He also called for better education of trainees and physicians on the use of genomic assays and interpretation of results from next-generation sequencing platforms.

“Trainees need to learn genomics as part of their general and subspecialty training,” Levine said. “Hematologists-in-training should rotate on diagnostic molecular pathology labs, as they do now with blood bank and hematopathology.”