According to a study published in the journal Blood, researchers at Washington University School of Medicine in St. Louis have demonstrated that an investigational drug called plerixafor makes chemotherapy more effective in treating acute myeloid leukemia, a cancer of the white blood cells.

The drug blocks these cells from binding to bone marrow by driving them into the bloodstream, where they are more susceptible to chemotherapy.

Geoffrey L. Uy, M.D., co-first author on the study and assistant professor of medicine, said:

“We’re usually very good at clearing these leukemia cells from the blood. But it’s much harder to clear these cancerous cells from the bone marrow.”

52 individuals with acute myeloid leukemia (AML) whose AML was resistant to the standard chemotherapy regimen or who had relapsed, were enrolled to participate in the combined Phase I and II clinical trial. All 46 participants in the Phase II section of the trial received plerixafor. The researchers found that all 46 participants achieved complete remission (no evidence of cancer was found in the bone marrow or blood following treatment).

Uy, who treats patients at the Alivn J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, explained:

“In general, we see complete remission rates between 20 and 30 percent. But a lot depends on individual patient characteristics.”

Results from earlier studies have demonstrated that mutations that cause AML may vary considerably among patients. Senior author, John F. DiPersio, M.D., Ph.D, the Virginia E. and Sam J. Golman Professor of Medicine, notes that all these leukemia cells, regardless of individual mutations, rely on the protective effects of the bone marrow.

DiPersio, who also treats people at the Siteman Cancer Center, said:

“With DNA sequencing identifying so many mutations that are unique to one patient, it may be very hard to find therapies that work directly on the cancer.

Instead, we are targeting a common pathway that all leukemic cells are addicted to – in this case, the relatively normal environment of the bone marrow.”

DiPersio continues:

“If these results are repeated in a larger study, it would be transformative. It would change the standard way we treat these patients – we would use this approach with everybody. In addition, the approach of targeting the tumor microenvironment could also be exploited for the treatment of other hematologic and solid tumor malignancies.”

Bone marrow protects leukemia cells by preventing the cell-suicide response that might cause them to self-destruct. Even though these cells do not divide rapidly in the bone marrow, they are extremely resistant to treatment. Although chemotherapy can remove leukemia from the bloodstream temporarily, “protected” AML cells in the bone marrow may cause the cancer to return.

Plerixafor prevents the AML cells from binding to the bone marrow, as a result the cells are pushed into the blood stream and begin to divide, making them more vulnerable to chemotherapy.

The U.S. Food and Drug Administration approved plerixafor in 2008 for use prior to a stem cell transplant to treat individuals suffering with non-Hodgkin’s lymphoma and multiple myeloma (two other types of blood cancer). In these two diseases, the drug is used to expel normal stem cells from the bone marrow into the bloodstream where they can then be collected for a transplant. For both these two cancers, returning the patient’s own stem cells following aggressive chemotherapy is a standard treatment.

DiPersio, explained:

“We helped in plerixafor’s development for stem cell mobilization. So we though if it makes normal stem cells leave the bone marrow to circulate, maybe it would do the same with leukemic cells.”

This concept proved to be effective in a study conducted in mice with a form of AML by DiPersio and his team in 2009. The team discovered that mice treated with plerixafor in addition to chemotherapy had improved survival compared with mice treated with chemotherapy alone. However, according to DiPersio, plerixador targets only one of the several chains attaching these cells to the bone marrow.

DiPersio, said:

“This is one of the first clinical examples of targeting the environment that leukemia cells live in. In the future, we may find other drugs, or combinations of drugs, that work better. There are now a number of groups around the world putting together similar approaches.”

Written by Grace Rattue