Further understanding of molecular and cytogenetic biomarkers may lead to more individualized treatment and, consequently, improved outcomes in acute myeloid leukemia, according to a researcher.
During a presentation earlier this year at the Acute Leukemia Forum in San Francisco, David Grimwade, MD, of the department of medical and molecular genetics at King’s College London School of Medicine, outlined the challenges associated with utilization of prognostic biomarkers in AML.
Grimwade emphasized the importance of reaching a consensus in the classification of prognostically relevant molecular and cytogenetic markers and the need to work toward understanding how the biology of leukemic stem cells interacts with the marrow microenvironment.
“These may yield the next generation of independent prognostic factors, predicting response to novel targeted therapies,” he said.
In a paper published in Current Opinion in Oncology, Grimwade and colleagues said significant improvements in technologies to detect minimal residual disease (MRD) have been achieved in the past 15 years. They reviewed recent studies showing that assessment of MRD using flow cytometric or molecular (real-time quantitative polymerase chain reaction) methods provides independent prognostic information. The results lend support to the further investigation of these assays within clinical trials, with the aim of developing more personalized treatment strategies.
“Dr. Grimwade has given us a nice summary of different prognostic markers,” Matt Kalaycio, MD, director of the Bone Marrow Transplant Program at Taussig Cancer Institute at Cleveland Clinic, told HemOnc Today. “Now we have to develop treatments toward the markers we have identified. The development of risk-directed strategies is an ongoing process.”
The clinical community has had success identifying populations of patients who will do well or poorly, but less success at developing new treatments for these stratifications of patients, Kalaycio said.
“For the patients with good prognostic factors, we have good treatments, but we do not have anything other than bone marrow transplant for the patients who have poor prognostic factors,” he said.
In addition, the model for treating AML has been to treat all cases of the disease the same way.
“Each of these prognostic categories represents individual leukemias, each of which requires specific therapies,” Kalaycio said. “In the future, someone will have leukemia, we will characterize it at the molecular level, and we will choose therapies based on that phenotype.”
There may be larger structural barriers to this kind of treatment, according to Kalaycio. He noted the model of the health care system in the United Kingdom.
“Every patient is treated on protocols that are agreed upon by the whole country,” he said. “In the United States, it is much more fractionated. People who get admitted to our clinic will get one regimen, whereas patients admitted to Ohio State, just 2 hours away, may receive something else. We won’t make strides fast enough with this model of treating acute leukemia.”
The problem is compounded because there is no financial incentive to send a patient to another facility for more personalized or technologically advanced treatment, Kalaycio said.
“At large centers, we are not fully reimbursed for treatment on cooperative group protocols,” he said. “Centers like ours lose money when we treat patients based on these new protocols. As health care dollars become more scarce, individual treatment may become less and less, which is what we do not want, particularly when we are discovering all of these individual markers in diseases like AML.”
Kalaycio said treating patients on the U.K. model is feasible but politically untenable.
“We have to keep searching for biomarkers, which is actually not incredibly difficult,” he said. “We need to build from the model of [acute promyelocytic leukemia] — which was an overwhelming success story — and motivate researchers to find other subtypes that are equally curable.”
- Grimwade D. Curr Opin Oncol. 2010;22:656-663.
- Smith ML. Blood Rev. 2011;25:39-51.
- Drs. Grimwade and Kalaycio report no relevant financial disclosures.