ATLANTA — Quizartinib is a promising treatment for refractory and relapsed acute myeloid leukemia (AML) after second-line chemotherapy or hematopoietic stem cell transplantation (HSCT), according to a cohort analysis of data from an open-label phase 2 safety and efficacy study presented during the 54th American Society of Hematology Annual Meeting and Exposition.

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FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITDs) are associated with early relapse and poor patient outcomes in AML patients receiving standard chemotherapy. But oral quizartinib (AC220), a FLT3 receptor tyrosine kinase inhibitor has shown promising activity in a Phase 1 study of patients with AML, noted lead author Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center’s Department of Oncology at Johns Hopkins University in Baltimore, MD.

The new analysis confirmed the high degree of activity of quizartinib monotherapy in FLT3-ITD(+) and FLT3-ITD(-) AML patients relapsed/refractory to second-line treatment or HSCT,  the study authors reported. “These data represent the highest level of single-agent activity observed to date for FLT3-targeted therapy in FLT3-ITD(+) relapsed/refractory AML. Of clinical significance in this heavily pretreated population, approximately one-third of patients were successfully bridged to potentially curative HSCT, and many patients who were refractory to prior therapy responded to quizartinib.”

The analysis was based on data from a phase 2 efficacy and safety trial of quizartinib monotherapy with a cohort of 138 patients >17 years with relapsed or refractory AML after second-line, salvage chemotherapy or HSCT; 100 (72%) were FLT3-ITD(+) and 38 (28%) were FLT3-ITD(-).

FLT3-ITD(+) patients had a median age of 50 years (range 19-17 years); FLT3-ITD(-) patients had a median age of 55 years (range, 30-73 years), the authors reported. The sexes of FLT3-ITD(+) patients were evenly distributed, but 61% of FLT3-ITD(-) patients were male.

Participants were administered quizartinib at an initial dose of 90 mg/day for females and 135 mg/day for males, and received continuous treatment for 28-day cycles, Dr. Levis reported.

Composite complete remission (CRc) rate was defined as complete remission (CR) plus complete remission with incomplete platelet recovery (CRp) plus complete remission with incomplete hematologic recovery (CRi).

CRc rates for FLT3-ITD(+) patients was 46% (6% CR+CRp; 40% CRi) with a median response duration of 12.1 weeks. Median overall survival (OS) for FLT3-ITD(+) patients was 22.9 weeks.

A total of 75% of FLT3-ITD(+) and 48% of FLT3-ITD(-) patients refractory to their last prior therapy achieved at least a partial response to quizartinib..

Among FLT3-ITD(-) patients, CRc was 32% (6% CR+CRp; 26% CRi), with a median response duration of 7.0 weeks. Median OS survival among FLT3-ITD(-) patients was 25.6 weeks. Among those who bridged to HSCT, median OS was not reached and 1-year survival was 64% vs a median OS of 20.8 weeks and a 1-year survival of 4% for those without an HSCT.A total of 33 patients (33%) survived more than 1 year; among FLT3-ITD(+) patients, 12 remained alive at last follow-up. An additional 12 (12%) had durable disease control (5+ months) with quizartinib.

Grade 3 or 4 hematologic treatment-related adverse events (AEs) were febrile neutropenia (40% vs 29%), anemia (26% vs 39%), and grade 3 or 4 thrombocytopenia/platelet count decreased (26% vs 21%). Grade 3 or 4 nonhematologic AEs occurring in ≥20% of patients (FLT[+] vs FLT[-]) included nausea (3% vs 3%), , QT interval prolongation (no grade 4; 8% vs 3%), vomiting (3% vs 3%), diarrhea (3% vs 5%), and fatigue (4% vs 0%).