The PROMISE of better therapy
How one UF researcher and her team are working to improve treatment for patients with acute myeloid leukemia
By April Frawley Lacey
During her postdoctoral training at the St. Jude Children’s Research Hospital, Jatinder Lamba, Ph.D., noticed something — much progress had been made in the treatment of acute lymphoblastic leukemia, but patients with the other common form of leukemia, acute myeloid leukemia, were not faring as well.
The disease is the second most common form of leukemia in children, yet it has the worst prognosis of all cancers in children.
“The outcome in acute myeloid leukemia is still very dismal,” said Lamba, an associate professor of pharmacotherapy and translational research in the College of Pharmacy. “Despite initial remission, the relapse rate is pretty high, with a significant proportion of patients experiencing relapse or refractory (not treatment-responsive) disease. Five-year overall survival varies from 30 percent in the elderly population to 60-70 percent in pediatric population. There is an unmet need to develop better treatment strategies to improve patient outcomes.”
A pharmacogenetic researcher by training, Lamba took on the challenge of discovering these new strategies in hopes of devising more effective treatments for patients with AML. She’s spent her career primarily focused on discovery and validation of pharmacogenomics biomarkers in hopes of understanding why treatments work in some patients and not in others.
After six years on the faculty of the University of Minnesota, Lamba came to UF in 2014, attracted to the university because of its reputation with personalized medicine. Led by College of Pharmacy Dean Julie Johnson, Pharm.D., UF’s personalized medicine program tailors treatments for patients with cardiovascular disease based on their genetic profile. This focus dovetails with Lamba’s own goal of developing personalized strategies for patients in treatment for AML.
Currently, her team is working on two NIH-funded projects. In September 2014, Lamba received a five-year, $1.55 million grant from the National Institutes of Health to study the most common therapeutic agent used in chemotherapy for AML — cytarabine, also known as ara-C.
Although ara-C is the most effective treatment for AML, outcomes vary greatly, with some patients developing resistance to it and others experiencing toxic effects.
“In most of the cases, development of resistance to the chemotherapy is one of the biggest challenge faced by clinicians,” Lamba said. “The relapsed disease is more aggressive and nonresponsive to chemotherapy.”
A major challenge in improving outcomes in AML how response to therapy differs from patient to patient. Although the reason is generally multifactorial, genetic factors, such as genetic variations, often play a significant role. Lamba’s team is studying how these variations, called single nucleotide polymorphisms or SNPs, affect how patients respond to treatment with ara-C and other agents used in leukemia. Identification of these SNPs may help in developing individualized treatment strategies that improve outcomes and reduce unnecessary toxicities and cost.
Using a novel statistical method she and her team developed called PROMISE (Projection Onto the Most Interesting Statistical Evidence), Lamba is trying to identify SNPs that can predict poor outcomes with ara-C chemotherapy.
Over time, Lamba hopes to establish a program for AML at UF Health that is similar to the personalized medicine program in place for cardiovascular disease treatment.
“This would present an opportunity to increase our accuracy in forecasting therapeutic outcomes in AML and allow more tailored, risk-stratified treatment approaches