Successful Combination Therapy for Aggressive Leukemia
2018-03-21 |

Successful Combination Therapy for Aggressive Leukemia

Acute myeloid leukemia (AML) is a cancer of the myeloid line of white blood cells, characterized by the rapid growth of abnormal cells that build up in the blood and bone marrow and interfere with the function of normal blood cells. Although it is a relatively rare disease, the incidence of AML increases with age. To date, the only treatment option is chemotherapy, which is effective in only 25-40%. Acute myeloid leukemia is a curable disease; however, the chance of cure for a given person depends on a number of prognostic factors.

Researchers from the Freiburg University Hospital have found a new, very effective therapy for the acute myeloid leukemia. In about every eighth AML patient, cancer cannot be repressed in the long term, neither with chemotherapy nor with the stem cell transplantation. The Freiburg researchers have now shown that these patients benefit from a combined treatment: they transferred T-immune cells from healthy donors and at the same time gave them a drug called sorafenib. Some of the patients were cured and in most of the cases, the disease was significantly suppressed. In detailed laboratory studies, the researchers discovered the treatment’s mode of action. Sorafenib makes the tumor cells “visible” for the immune cells that are aimed to fight against them. Therefore, immune cells are able to destroy cancer more effectively. The laboratory results were confirmed by data from more than 400 patients from 39 study centers worldwide. The study was published on February 12 this year in the journal Nature Medicine.

AML is the most common form of adult leukemia. Around one in four sufferers has a gene mutation that makes cancer resistant to chemotherapy. Transplantation of immune stem cells from healthy donors leads to healing in near half of these patients. Nevertheless, in almost 60 percent of those, cancer can recur, which is usually more aggressive. In those patients, in whom leukemia was repeated, the new therapy can be extremely helpful.

"Originally, sorafenib was only given to patients to slow the progression of the disease. We then found that cancer disappears in patients who had previously received a transplant of healthy immune cells. That surprised us, "says study leader Dr. Robert Zeiser, the Senior Physician and Head of the Department of Tumor Immunology at the University Medical Center Freiburg.

The team led by Prof. Zeiser demonstrated the clinical findings in the laboratory and showed that sorafenib in leukemia cells stimulates the production of the messenger-molecule interleukin-15. This interferes with the “camouflage” mechanisms of cancer cells and makes them susceptible to the immune system. "The transplanted, healthy immune T cells recognize the cancer cells in this way and kill them. In addition, the transplanted cells live longer due to the messenger-molecule and can destroy more cancer cells, "says the first author of the study Nimitha Mathew, biotechnologist in the team of Prof. Zeiser at the Department of Internal Medicine of the University Hospital Freiburg.

In addition to the laboratory data, the researchers from Freiburg coordinated a large-scale analysis of 409 patients from 39 study centers in Europe, the USA, Australia and Asia. The patients were all treated with various drugs due to an AML leukemia relapse. "The combination of sorafenib and T-cell transmission clearly led to the much higher chance of survival," says Prof. Zeiser.

Sorafenib is already approved for the treatment of liver, kidney and thyroid cancer. So far, it has been known to stop the proliferation of certain cancer cells and inhibit the blood supply to the tumor. "Because sorafenib is already approved, those affected can be treated immediately," explains Prof. Zeiser.

"The study is an excellent example of the often-demanded translation in the medical research. The motivation came from observations on patients, was examined in the laboratory and then re-examined in the clinic," says Dr. Justus Duyster, Medical Director of the Department of Internal Medicine I of the University Medical Center Freiburg.

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