Pretreatment FMS like Tyrosine kinase-3 Internal Tandem duplication (FLT3-ITD) Mutant Allele Burden Does Not Predict Response to the Combination of Sorafenib and Azacytidine in Patients with Relapsed or High Risk Elderly Untreated Acute Myeloid Leukemia

To evaluate if pretreatment FLT3-ITD allele burden is associated with an impact on the response to the combination of sorafenib and azacytidine. Methods: We retrospectively analyzed the clinical records for 56 patients with FLT3-ITD treated with azacytidine and sorafenib between 2009 and 2013. Results: Among the patient, 34 (54%) were male, 15 (24%) had secondary AML and 7 (11%) had therapy-related AML. The median age prior to treatment with azacytidine plus sorafenib was 64 years (range, 20-87), with the median age at initial diagnosis of 63 years (range, 19-86 years). Eastern Cooperative Oncology Group performance status was 2 in 19 patients (31%). The median number of prior therapies received was 2 (range, 0-9); 12 patients were elderly (aged 61 years) without prior therapy who were deemed unfit to receive standard cytotoxic chemotherapy. The median white blood count was 8.9 10 (range, 7.5-13.1 10) and the median bone marrow blast percentage was 56% (range, 0-99%). The median FLT3-ITD allelic burden was 0.73 (range, 0.34-0.93) Median time from diagnosis to treatment with sorafenib and azacytidine was 5.5 months (range, 3 days -27months); cytogenetics was unfavorable in 8 patients (13%), normal karyotype in 30 (48%), and miscellaneous in 24 (39%). Eight (14%) patients achieved a complete response (CR) with 7 patients (13%) achieving CR without platelet recovery (CRp) and 10 (18%) achieving CR without peripheral blood count recovery (CRi); 1 patient (1%) had partial response (PR). The overall response rate was 46%. The OS at 3 months and 12 months were 45% and 24%, respectively. FLT-3 ITD allele burden had no significant impact on overall survival (OS) [HR 0.93, 95% CI (0.79-1.10); p1⁄40.433]. The variables with significant and independent impact on OS were achieving CR/CRp/CRi [HR 0.183, 95% CI (0.77-0.435); p 1⁄4 0.000], and ECOG 2[HR 3.78, 95% CI (1.782-7.843)]. The only variable with a significant impact on the overall response rate was blast percentage [OR 1.025 (1.007-1.043); p 1⁄4 0.007]. FLT3-ITD allele burden had no impact on response rate [OR 0.63 (0.21-1.83) p 1⁄4 0.394]. Conclusion: The FLT3-ITD allele burden in patients with relapsed, refractory, or high-risk untreated AML does not have an impact on the response rate or survival.