Wilmot Cancer Institute research shows that giving antibody therapy more often but at lower doses — and perhaps teaching patients how to inject themselves at home — could be a future option for people with chronic lymphocytic leukemia (CLL) and other blood cancers that commonly afflict older adults.
Scientists discovered the new treatment approach as they were investigating better ways to measure the effectiveness of some of the newest drugs for blood disorders. In their study, they determined that the high-frequency/low-dose strategy may be less toxic but just as powerful for fighting cancer. The research, led by Clive Zent, M.D., a professor of Hematology/Oncology and Medicine at the University of Rochester Medical Center and Wilmot, was published by Cancer Immunology Research.
Based on the laboratory work, Zent and Paul Barr, M.D., are designing a new clinical trial for 2019 to evaluate their high-frequency-low-dose-at-home approach in patients needing initial treatment for CLL. It will be funded by Acerta/AstraZeneca.
A standard treatment for CLL is rituximab injections. The drug is an antibody that coats the cancer cells, effectively marking them, and then allowing immune cells known as macrophages to “eat” up the marked cancer cells. Rituximab was approved for this use in 1997. Original tests of the drug called for administering high doses to target the cancer. However, Zent said, his laboratory discovered that the same effect can be achieved with concentrations of less than 1% of those currently considered to be therapeutic.
The process in which immune cells kill the antibody-coated cancer cells is called antibody dependent cellular phagocytosis (ADCP) — and Zent believes his research suggests that testing all new CLL drugs for their ability to induce ADCP should be the new standard.
“Our new treatment method could be more effective and convenient, with lower toxicity and costs,” Zent said. “Patients could have less risk of unpleasant side effects and they could learn how to give themselves their injections at home. This could change the way we treat CLL patients because they would not need to undergo long intravenous infusions in medical facilities.”
Other clinical trials have also shown that high-frequency-low-dose regimens may be less likely to cause acquired resistance to the drug, Zent said.
He and Barr, who is the medical director of Wilmot’s Clinical Trials Office, are also evaluating new combinations of other novel drugs for CLL to seek shorter courses of treatment. The research team includes University of Rochester scientist Michael Elliott, PhD., an associate professor of Microbiology and Immunology; Charles Chu, Ph.D., a Wilmot research associate professor; Andrea Baran, M.S., an associate in Biostatistics; and first author Karl VanDerMeid, a technical associate in Zent’s lab who conducted most of the experiments.