Effect of Cytarabine/Anthracycline/Crenolanib Induction on MRD in Newly Diagnosed FLT3 Mutant AML

Conference Correspondent - ASCO 2017 - Acute Myeloid Leukemia

In acute myeloid leukemia (AML), patients who are positive for the FLT3-ITD mutation have been reported to have a particularly poor prognosis. Elimination of FLT3-positive clones may lead to reduced relapse rates. Crenolanib, a type I FLT3 tyrosine kinase inhibitor, inhibits both FLT3-ITD and TKD mutations. In this study, researchers found that a single induction cycle of crenolanib in combination with cytarabine/anthracycline leads to minimal residual disease (MRD) negativity and a low rate of early relapse in patients with newly diagnosed FLT3-positive AML.

A total of 32 evaluable patients with newly diagnosed, FLT3-positive AML received induction treatment with cytarabine 100 mg/m2 daily for 7 days and either daunorubicin (90 mg/m2 if <60 years of age; 60 mg/m2 if ≥60 years of age) or idarubicin 12 mg/m2 for 3 days. Crenolanib 100 mg 3 times daily was started on day 9 until 72 hours prior to the next chemotherapy.

MRD data were available in 24 patients, of whom 20 (80%) became MRD-negative after treatment. After a median follow-up of 8.2 months, 16 (80%) patients remain relapse-free. Patients aged ≥60 years were associated with higher MRD-negative complete remission and lower relapse rate.

The data suggest that crenolanib administered in combination with standard induction is associated with a high rate of achieving an MRD-negative state and a low rate of relapse in previously untreated adults with mutant FLT3. Although these findings are promising, further research is needed to determine whether treatment with a crenolanib-containing regimen is superior to treatment with standard chemotherapy alone.

Stone RM, et al. ASCO Abstract 7016.

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Last modified: June 6, 2017
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