Comparable outcomes with gilteritinib or quizartinib in R/R AML

In patients with relapsed or refractory (R/R), FLT3-ITD-positive acute myeloid leukaemia (AML) and similar baseline characteristics, both gilteritinib and quizartinib were generally well tolerated and associated with improved survival and treatment response compared with salvage chemotherapy [1].

Based on findings from the phase 3 ADMIRAL trial [2], gilteritinib is approved for patients with R/R FLT3-mutated AML. The phase 3 QuANTUM-R trial demonstrated the benefit of quizartinib in patients with R/R AML with FLT3 internal tandem duplication (FLT3-ITD) mutations [3]. Eligibility criteria across both studies were similar, however, QuANTUM-R was stricter regarding prior therapy intensity and remission duration.

The current posthoc analysis, presented by Dr Alexander Perl (University of Pennsylvania, USA), described outcomes from ADMIRAL among patients who otherwise met eligibility for QuANTUM-R [1]. In the matched intention-to-treat (ITT) population from the ADMIRAL study, 66% of patients were preselected for high-intensity salvage chemotherapy compared with 77% in the ITT population of the QuANTUM-R study. Demographic and baseline characteristics of the matched ADMIRAL ITT population and QuANTUM-R ITT population were similar.

Rates of haematopoietic stem cell transplantation (HSCT) were comparable in patients treated with gilteritinib (35%) or quizartinib (32%), as were the proportions of patients who resumed gilteritinib (23%) or quizartinib (20%) therapy post-HSCT. Median overall survival (OS) in patients treated with gilteritinib or quizartinib was longer than that observed with salvage chemotherapy. After a median follow-up of 17.4 months, median OS was 10.2 months with gilteritinib versus 5.6 months with chemotherapy (HR 0.573; P=0.0008). After a median follow-up of 23.5 months, median OS was 6.2 months with quizartinib versus 4.7 months with chemotherapy (HR 0.760; P=0.02). Responses to gilteritinib and quizartinib, as measured by composite complete remission (CRc), were similar. Median time to achieve CRc was 1.8 months with gilteritinib and 1.1 months with quizartinib, median duration of CRc was 5.5 months with gilteritinib and 2.8 months with quizartinib. The safety profiles of gilteritinib and quizartinib were generally similar.

Although cross-study comparisons have substantial limitations, these findings suggest that while remission is achieved faster with quizartinib, response may be more durable and survival potentially longer with gilteritinib.

1. Perl AE, et al. Clinical Outcomes Following Treatment with Gilteritinib or Quizartinib in Patients with Relapsed/Refractory FLT3-ITD+ Acute Myeloid Leukemia. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 995.
2. Perl AE, et al. N Engl J Med. 2019;381:1728-40.
3. Cortes JE, et al. Lancet Oncol. 2019;20:984-97.

Posted on 18 February 20214 September 2023