Personalized Drug Screen Aids Treatment Selection for Patients with Multiple Myeloma
A personalized testing method may quickly and more accurately predict the effectiveness of a treatment for multiple myeloma in individual patients. The process, described in Biomaterials (doi:10.1016/j.biomaterials.2015.09.017), may also aid patients with leukemia or lymphoma.
The screening method suggests which commonly prescribed multiple myeloma drug or combination of drugs should be considered first for a particular patient. The test also suggests optimum dosage.
The method is being evaluated in a clinical trial involving patients with the bone marrow cancer. Trial results will indicate if the method is more effective than current screening methods.
"Even before the patient completes all of the MRIs, CT scans, and other imaging procedures following diagnosis, we can have a recommendation for which drug and dosage to prescribe," said corresponding author Kareem Azab, PhD, an assistant professor of radiation oncology at the School of Medicine and the Siteman Cancer Center at Washington University School of Medicine in St. Louis, Missouri. Test results are available in 3 to 4 days.
Multiple myeloma is a cancer of the infection-fighting plasma cells, part of the immune system found mainly in bone marrow. The disease will be diagnosed in an estimated 26 850 people in the United States in 2015 and approximately 11 240 patients are expected to die, according to the American Cancer Society. Half of patients with multiple myeloma diagnosed in the earliest stage of the disease do not survive beyond approximately 5 years after initial treatment because the cancer becomes resistant to treatments.
Multiple myeloma is difficult to treat because 90% of patients have no obvious genetic mutation that can be targeted with treatment. In addition, standard drug screening methods do not adequately recreate the environment surrounding cancer cells a particular patient's body, making those methods less reliable at predicting effectiveness of drug therapies.
Azab hopes a more personalized approach will improve long-term patient outcomes. The method relies on 3-dimensional tissue-engineered bone marrow (3DTEBM) cultures that Azab and his colleagues developed using bone marrow samples from patients with multiple myeloma.
To more closely mimic what goes on within the body, scientists take small samples of a patient's cells, both cancerous and benign, and remodel them in the laboratory. This tumor microenvironment includes the cancer cells and other neighboring blood vessels, immune cells, and other components whose interaction can help or inhibit tumor cells' growth.
Drugs are then tested on the remodeled cells to determine which treatment is likely to be most effective for that patient.
Azab's method gauges the sensitivity of a patient's cells to different drugs at any time in the course of the disease, thereby continued screening as a patient's disease becomes more resistant to a particular treatment could suggest changing to a different therapy. This could save valuable time, he said.
"Now we have a drug test that closely replicates what's going on with a patient at any given moment," Azab said. "We think this method has a better chance of working than existing options."
Azab and his colleagues have launched a company, Cellatrix, in coordination with Washington University's Office of Technology Management and BioGenerator, a nonprofit organization that helps area bioscience companies with their development process.