Gilteritinib and Prior Midostaurin/Sorafenib Aids Clinical Response in Patients with FLT3-Mutated AML

Gilteritinib (Xospata) monotherapy reacts favorably and led to higher rates of composite complete remissions (CCR) in patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) who received prior midostaurin (Rydapt) or sorafenib (Nexavar). This analysis was conducted retrospectively, evaluating data from the CHRYSALIS (NCT02014558) and ADMIRAL (NCT02421939) trials.¹

CCR rates were similar across both trials when comparing patient who received gilteritinib and prior tyrosine kinase inhibitor (TKI) therapy or gilteritinib and no prior TKI therapy. Patients in the CHRYSALIS study who received prior TKI therapy (n = 33) had a CCR of 42% and patients who did not receive prior TKI therapy (n = 112) had a CCR rate of 43%. Patient in the ADMIRAL trial who received gilteritinib and prior TKI therapy (n = 33) had a CCR rate of 52% and those who received gilteritinib and no prior TKI therapy (n = 214) had a CCR rate of 55%. Patients in the ADMIRAL trial who underwent salvage chemotherapy and had previous TKI therapy (n = 15) had a CCR rate of 20% and those who underwent salvage chemotherapy and did not have precious TKI therapy (n = 109) had a CCR rate of 22%.

Patients in the CHRYSALIS trial only received sorafenib as the TKI agent. The ADMIRAL trial evaluated patients who received sorafenib or midostaurin as TKI agents. Patients in this trial who received gilteritinib and midostaurin (n = 14) had a CCR of 57% and those whose prior TKI was sorafenib (n = 19) had a CCR of 47%. In the group of patients who underwent salvage chemotherapy and received the prior TKI agent, midostaurin, (n = 9) had a CCR of 33% and patients who received sorafenib in this group (n = 6) showed no CCR.

The phase 1/2 CHRYSALIS dose-escalation/expansion trial enrolled patients to receive 20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg doses of gilteritinib once a day for 28 cycles The 120 mg and 200 mg dose cohorts were expanded to include patients with FLT3 mutations.

The phase 3 ADMIRAL trial evaluated patients with R/R FLT3-mutated AML and randomized them 2:1 to receive 120 mg of gilteritinib or salvage chemotherapy. Treatment was administered in 28-day cycles.

The CHRYSALIS trial demonstrated similar median overall survival (OS) rates between patients who did or did not receive prior TKI treatment. The median OS for patients in the prior TKI group was 7.2 months and the median OS for patients without prior TKI treatment was 7.5 months.

In the ADMIRAL trial, patients who received gilteritinib and prior TKI therapy had a median OS of 8.7 months and patients who received gilteritinib without prior TKI therapy had a median OS of 9.5 months. Patients who received salvage chemotherapy and received prior TKI treatment had a median OS of 5.1 months and those who did not receive prior TKI therapy had a median OS of 6.1 months.

The median age of patients in the CHRYSALIS trial who received prior TKI treatment was 56 years (range, 24-84), 55% of patients were female, 67% had an ECOG performance status of 0 or 1, and 33% had an ECOG PS of 2 or greater. Patients without prior TKI treatment in this trial had a median age of 61 years (range, 22-87), 53% were female, and 78% had an ECOG performance status of 0 or 1.

Patients in the ADMIRAL trial who received gilteritinib and prior TKI treatment had a median age of 55 years (range, 20-82), 42% were female, and 76% had and ECOG performance status of 0 or 1; whereas those who did not receive prior TKI therapy had a median age of 62.5 years (range, 22-84), 55% were female, and 85% had an ECOG performance status of 0 or 1. Patients who received salvage chemotherapy and prior TKI treatment had a median age of 64 years (range, 34-78), 60% were female, and 93% had an ECOG performance status of 0 or 1; whereas those who did not receive prior TKI therapy had a median age of 61 years (range, 19-85), 56% of patients were female, and 84% had an ECOG performance status of 0 or 1.

Both sorafeniband midostaurinin the frontline setting revealed favorable responses in patients with FLT3-mutated AML with gilteritinib. These data suggest further studies in this treatment area with larger patient populations to confirms these findings.

_REFERENCE

_{Perl A, Hosono N, Montesinos P, et al. Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Blood Cancer J. 2022;12(5):84. doi: 10.1038/s41408-022-00677-7}