The final data from a phase II study confirmed the high degree of activity of quizartinib monotherapy in persons with acute myeloid leukemia (AML), with disease cleared from the bone marrow in more than one-third of the group, researchers reported at the annual meeting of the American Society of Hematology, held in Atlanta, Georgia, December 8–11, 2012.            

Quizartinib, also known as AC220, blocks the FLT3 enzyme. Produced by the FLT3 gene, the enzyme signals bone-marrow stem cells to divide and replenish, according to a statement issued by Johns Hopkins Medicine, Baltimore, Maryland. In approximately 25% of persons with AML, the disease mutates FLT3 so that the enzyme stays on permanently. This causes rapid growth of leukemia cells, making treatment more difficult.

“An FLT3-ITD mutation tells us that, typically, patients will need very intensive chemotherapy just to achieve a remission, and then the disease will regrow quickly,” affirmed the study’s lead investigator, Mark Levis, MD, PhD, in the Johns Hopkins statement. Levis is a member of the Department of Oncology at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

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The newly reported portion of the international clinical trial focused on 137 persons with AML relapsed or refractory to second-line, salvage chemotherapy or relapsed after hematopoietic stem cell transplantation. A total of 99 patients (72%) were FLT3-ITD-positive (median age 50 years; range 19 to 77 years), and 38 (28%) were FLT3-ITD-negative (median age 55 years; range 30 to 73 years).

Women received quizartinib at a starting dose of 90 mg/day, and men received a dose of 135 mg/day, for 28-day cycles. The composite complete remission (CR) rate (CRc) consisted of CR, CR with incomplete platelet recovery (CRp), and CR with incomplete hematologic recovery (CRi).

For the FLT-ITD-positive patients, CRc was 44% (4% CR, 0 CRp, and 40% CRi). Median duration of response was 11.3 weeks and median overall survival was 23.1 weeks. Among persons in this group refractory to their last AML therapy, 47% achieved a CRc with quizartinib.

Among the FLT3-ITD-negative patients, the CRc rate was 34% (3% CR, 3% CRp, and 29% CRi). Median duration of response was 5 weeks and median overall survival was 25.6 weeks. Among persons in this group refractory to their last AML therapy, 31% achieved a CRc with quizartinib.

Long-term survival from the therapy is still unknown. However, after quizartinib cleared leukemia from the bone marrow, 47 patients (34%) were able to undergo bone-marrow transplantation, and some have survived for 2 years after treatment with no disease recurrence.

The most common treatment-related adverse effects were nausea in 38% of patients, anemia (29%), QT interval prolongation (26%), vomiting (26%), febrile neutropenia (25%), diarrhea (20%), and fatigue (20%). The most common grade 3 or grade 4 treatment-related adverse effects were anemia (26%), febrile neutropenia (25%), thrombocytopenia (15%), neutropenia (12%), and QT interval prolongation (10%). A total of 14 patients (10%) experienced a treatment-related adverse effect resulting in drug discontinuation.