Abstract
7012 Background: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) is associated with early relapse after chemotherapy and poor survival. Relapse after HSCT or failure of salvage chemotherapy in FLT3-ITD AML is rarely associated with subsequent HSCT or durable survival. Quizartinib, an oral FLT3 inhibitor, shows promising activity; a Ph 2 study (n=333) of quizartinib monotherapy (Levis et al, ASH 2012) reported that quizartinib often bridged patients (pts) to HSCT. Methods: 136 FLT3-ITD(+) and 40 FLT3-ITD(-) pts, relapsed/refractory after HSCT or 1-second line regimen, were included. The response category of composite complete remission (CRc) comprised complete remission [CR] + complete remission with incomplete platelet recovery [CRp] + complete remission with incomplete hematologic recovery [CRi]. Results: Quizartinib was discontinued for HSCT in 47/136 FLT3-ITD(+) pts (35%), with 44/47 having at least a PR (2 CRp, 24 CRi, 18 PR). Median overall survival (OS) was 41.5 wks for pts with CRc prior to HSCT and 29 wks for pts with PR. The 1y survival rate was 39% for both response groups. Pts with a CRc (n=36) or PR (n=20) but no HSCT, respectively, had a median OS of 24.5 and 20.9 wks and 1y survival rates of 25% and 5%. Of 27 pts with OS >52 wks, 17 (63%) had HSCT. Quizartinib was discontinued for HSCT in 14/40 FLT3-ITD(-) pts (35%), with 13/14 having at least a PR (1 CR, 1 CRp, 7 CRi, 4 PR). Median OS was not yet reached for pts with CRc, and was 40.7 wks for pts with PR. The 1y survival rate was 78% for pts with CRc and 50% for pts with PR. 8 of these 14 pts had detectable ITD mutation but the level was below the prespecified 10% cutoff. Conclusions: Of clinical significance in these heavily pretreated pts who had failed salvage chemotherapy or HSCT, approximately 1/3 were successfully bridged to potentially curative HSCT, with encouraging 1y survival rates. To extend the potential benefits of FLT3 inhibitor therapy in combination with allogeneic HSCT, studies of maintenance quizartinib to prevent relapse post HSCT are ongoing. Clinical trial information: NCT00989261.
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