AML-091: Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib

Abstract

<h3>Context:</h3> Findings from the phase 1/2 CHRYSALIS trial and the phase 3 ADMIRAL trial demonstrated the safety and efficacy of the <i>FLT3</i> inhibitor gilteritinib in patients with FLT3-mutated (<i>FLT3^Mut</i>⁺) relapsed/refractory (R/R) AML. The efficacy of gilteritinib after prior tyrosine kinase inhibitor (TKI) therapy in these patients is unclear. <h3>Objective:</h3> Determine whether prior TKI therapy affected response and survival in <i>FLT3^Mut</i>⁺ R/R AML patients treated with gilteritinib. <h3>Design:</h3> A retrospective analysis of the CHRYSALIS and ADMIRAL trials. <h3>Patients:</h3> We retrospectively analyzed outcomes in patients with R/R AML previously treated with TKIs (midostaurin/sorafenib), before receiving 120 or 200 mg gilteritinib. <h3>Main Outcomes Measures:</h3> Treatment response and overall survival (OS) in patients who previously received or did not receive treatment with TKIs. <h3>Results:</h3> Of the 145 FLT3-mutation-enriched patients who received 120- or 200-mg gilteritinib in the CHRYSALIS trial, 33 (23%; 120 mg, n=15; 200 mg, n=18) had received a prior TKI (all sorafenib). Rates of composite complete remission (CRc) in patients who received prior TKIs (42%) and those who did not (43%) were similar. Among patients who received prior TKIs, rates of CRc were 53% in the 120 mg group and 33% in the 200 mg group; rates of CRc in patients without prior TKIs were similar across dose groups (44% and 42%, respectively). In the ADMIRAL trial, 31 of 247 (13%) R/R <i>FLT3^Mut</i>⁺ AML patients in the gilteritinib arm and 14 of 124 (11%) patients in the salvage chemotherapy (SC) arm had received prior TKIs. In the gilteritinib arm, CRc rates were comparable in patients who received (48%) and did not receive prior TKIs (55%); lower CRc rates were observed in the SC arm in both TKI and non-TKI pretreated groups (21% and 22%, respectively). Median OS in patients treated with prior TKIs was 6.5 months with gilteritinib and 4.7 months with SC (HR=0.671 [95% CI: 0.328, 1.376]); in patients without prior TKIs, median OS was 9.6 and 6.0 months, respectively (HR=0.625 [95% CI: 0.474, 0.824]). <h3>Conclusion:</h3> High response rates with gilteritinib were observed in patients with <i>FLT3^Mut</i>⁺ R/R AML who received prior TKIs.