Gilteritinib in R/R AML patients priorly treated with midostaurin or sorafenib

The oral FLT3 inhibitor gilteritinib demonstrated efficacy and safety in patients with FLT3-mutated relapsed or refractory (R/R) acute myeloid leukaemia (AML). Its safety and antileukaemic activity as a single agent in an FLT3 mutation-enriched R/R AML population was initially documented in the phase 1/2 CHRYSALIS trial [1]. The subsequent phase 3 ADMIRAL trial demonstrated that gilteritinib treatment was associated with a longer median overall survival (OS) in FLT3-mutated patients compared with salvage chemotherapy [2].

Dr Alexander Perl (University of Pennsylvania, USA) retrospectively determined whether prior therapy with the tyrosine kinase inhibitors (TKIs) midostaurin or sorafenib affected treatment response and survival in patients with FLT3-mutated R/R AML treated with gilteritinib in the CHRYSALIS and ADMIRAL trial [3].

In the CHRYSALIS trial, high response rates with gilteritinib were observed in heavily pretreated FLT3 mutation-enriched patients. Rates of composite complete remission (CRc) were similar in patients who received prior TKIs (42%) and in those who did not (43%). Higher response rates with gilteritinib than with salvage chemotherapy were observed in prior TKI-treated patients with FLT3 mutations in the ADMIRAL trial. 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 salvage chemotherapy arm in both TKI-treated and non-treated groups (21% and 22%, respectively). Remission was achieved in patients with FLT3-ITD, FLT3-TKD, or both.

Among patients who received prior midostaurin or sorafenib, longer survival was observed in patients treated with gilteritinib than in those treated with salvage chemotherapy. Median OS in patients treated with prior TKIs remained high in patients treated with gilteritinib compared with those treated with salvage chemotherapy, but differences were not significant (6.5 vs 4.7 months; HR 0.671). In patients who did not receive prior TKIs, median OS was 9.6 months in the gilteritinib arm and 6.0 months in the salvage chemotherapy arm (HR 0.625).

1. Perl AE, et al. Lancet Oncol. 2017;18:1061-75.
2. Perl AE, et al. N Engl J Med. 2019;381:1728-40.
3. Perl AE, et al. Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 334.

Posted on 18 February 20214 September 2023