A new experimental drug induced remission in high-risk leukemia patients

Remission in high-risk leukemia patients

According to a study led by researchers at the Johns Hopkins Kimmel Cancer Center, a new drug to treat acute myeloid leukemia, which was tested in Phase 2 clinical study, has shown efficacy in more than one third of patients. According to  researchers, Quizartinib or AC220, the new drug, gave results in patients who have not responded to previous treatments.

Acute myeloid leukemia, the most common form of leukemia, is a cancer of the blood cells that occurs through uncontrolled proliferation of immature cells. Signs and symptoms of leukemia include fever, fatigue, bone pain, weight loss. Symptoms appear due to neutropenia, ie low levels of neutrophils, thrombocytopenia, decreased platelets levels, and anemia, which means low erytrocytes level. These symptoms are pallor, dyspnea, asthenia, infection, bleeding, and more.

Leukemia Patients

Treatment is primarily aimed at cleaning bone marrow of leukemic cells and then bone marrow transplantation. Sometimes after initial response to treatment, patients  become resistant and they need to try other drugs. Mark Levis, MD, Ph.D., lead investigator on the study and associate professor of oncology and medicine at Johns Hopkins, said chemotherapy induces remission in more than two-thirds of patients but  about 50% of these relapse, and the end is usually fatal. He added that AC220 has helped many patients receive marrow transplantation and that even they were amazed at how well it worked this drug in these patients.

The study conducted by researchers at the Johns Hopkins Kimmel Cancer Center included 137 patients with AML with FLT3 mutation. Levis stressed that FLT3-ITD mutation is a marker of aggressive disease. Patients with this mutation require intensive chemotherapy and the disease usually recurs. Quizartinib, or AC220, blocks the enzyme responsible for the division of bone marrow stem cells, and is available in oral form. Levis added that the drug begins to take effect after 2 days and in 60 days the bone marrow is completely free of AML cells.

The 137 participants with resistant AML enrolled in the study received between 90 and 135 mg of Quizartinib for 28 days. Of those with  FLT3-ITD, 44% had some form of clinical remission, noting that they had still need blood transfusions. Also, 34% of those at which the mutation was not detectable had the same type of response. The most common side effects were nausea, vomiting, diarrhea, febrile neutropenia, fatigue etc, 10% of participants being forced to discontinue treatment due to side effects.

The researchers said they want to lower Quizartinib doses to minimize side effects and that the next step is to test it in Phase III trials.