Combination of Gilteritinib and Allo HSCT Improves Survival in FLT3-Mutated AML

Publication
Article
Targeted Therapies in OncologyJuly 1, 2023
Volume 12
Issue 9
Pages: 41

Gilteritinib can be a promising bridge to allogeneic hematopoietic stem cell transplantation, according to data at the European Society for Blood and Marrow Transplantation 49th Annual Meeting.

Findings from a real-world study evaluating the combination of gilteritinib (Xospata) and allogeneic hematopoietic stem cell transplantation (allo HSCT) show that adding the agent can improve outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML).

Specifically, gilteritinib can be a promising bridge to allo HSCT, according to Desiree Kunadt, MD, who presented the data at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting. Kunadt and colleagues further observed improved survival in patients who received gilteritinib maintenance after undergoing allo HSCT.1

A total of 156 patients from 25 hematologic centers around the world were enrolled. Sixty-nine patients were primary refractory and 87 were relapsed. Patients with FLT3 internal tandem duplication (FLT3-ITD) mutation or FLT3 tyrosine kinase domain (FLT3-TKD) mutation were stratified into 3 groups: gilteritinib monotherapy (n = 116), gilteritinib plus allo HSCT (n = 23), and allo HSCT plus gilteritinib maintenance (n = 17).

Patients who underwent allo HSCT after gilteritinib treatment had a 2-year overall survival (OS) probability of 75% (95% CI, 59%-97%) from allo HSCT. Patients who received gilteritinib as maintenance therapy after allo HSCT had a 2-year OS rate of 90% (95% CI, 73%-100%).

Two-year radiographic progression-free survival (rPFS) was lowest in the gilteritinib-only group (24%; 95% CI, 15%-37%). Better rates were observed when gilteritinib was followed by allo HSCT (44%; 95% CI, 18%-100%) and administered as maintenance after allo HSCT (74%; 95% CI, 52%-100%).

“Overall survival was longest when patients received gilteritinib maintenance after the allo HSCT and…was shortest when patients received gilteritinib only,” said Kunadt, a member of the Faculty of Medicine Carl Gustav Carus at Dresden University of Technology in Germany.

The median age of patients was 58.5 years (range, 21-84), and the majority were women (57.1%). Most patients had 0 (53.8%) or 1 (34.6%) prior treatment with an FLT3 inhibitor. “Most of the patients were initially stratified as intermediate or adverse risk at first diagnosis, and 88% of patients were considered fit enough for intensive induction therapy,” Kunadt said.

Characteristics of Treatment With Gilteritinib

Characteristics of Treatment With Gilteritinib

Kunadt reported that 23.1% of patients (36/156) had received gilteritinib before allo HSCT and 10.9% (17/156) had received it as maintenance after allo HSCT. As shown in the TABLE,1 the duration of gilteritinib treatment before allo HSCT was 2.35 months (range, 0.66-30.83) and of gilteritinib maintenance after allo HSCT was 16.6 months (range, 1.87-28.1).

OS was 5.19 months (range, 0.62-60.17) in the gilteritinib-only group, 10.35 months (range, 1.74-29.02) in the allo HSCT group, and 16.79 months (range, 1.28-33.26) in the maintenance group (P < .001). Event-free survival (EFS) was 3.83 months (range, 0.49-60.17) in the monotherapy group, 10.35 months (range, 1.74-29.02) in the allo HSCT group, and 14.85 months (range, 0.13-33.26) in the maintenance group (P < .001). CR/CRi was 37.1% (43/116) in the monotherapy group, 34.8% (8/23) in the allo HSCT group, and 70.6% (12/17) in the maintenance group (P = .0027).

Investigators focused on patients who had been salvaged with gilteritinib and subsequent allo HSCT and patients who had received gilteritinib only and not undergone allo HSCT. “OS was significantly improved when patients received sequential allo HSCT after gilteritinib compared with… gilteritinib only…, with a hazard ratio of 3.7 [95% CI, 1.7-7.9; P < .001],” Kunadt said. “Similar results were evaluated for EFS, which was also significantly improved for the allo HSCT group, with a hazard ratio of 5.6 [95% CI, 2.8-11.4; P < .0001].”

Multivariate analysis showed that therapy-related AML was an independent risk factor for worse OS, and a high Karnofsky score was associated with better EFS.

When comparing the 2 gilteritinib monotherapy subgroups (ie, patients who had previously received allo HSCT and patients who had not), the “analysis revealed no significant difference in overall survival between…[them]. The 1-year overall survival rates were 38% and 22%, respectively,” Kunadt said.

A high Karnofsky score appeared to be an independent factor for better OS and EFS, and previous allo HSCT to be beneficial for improved EFS.

Although the prognosis for patients with relapsed/refractory AML with an FLT3 mutation is dismal, the condition may be mitigated with gilteritinib/allo HSCT combination therapy, and gilteritinib is a promising bridge to allo HSCT, Kunadt concluded.

REFERENCE
1. Kunadt D. Gilteritinib and allogeneic hematopoietic stem cell transplantation improve outcome in relapsed/refractory FLT3-mutated AML: real-world data from a multicenter analysis. Presented at: 49th European Bone Marrow Transplantation Annual Meeting; April 23-26, 2023; Paris, France. OS01-01.
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