Gilteritinib as post-transplant maintenance for acute myeloid leukemia with FLT3 internal tandem duplication mutation.

Original message:

In this randomized clinical trial, patients with acute myeloid leukemia (AML) who had a FLT3 ITD mutation in first remission after stem cell transplantation were randomized to receive maintenance therapy with placebo or gilteritinib for 24 months. Was assigned randomly. Although gilteritinib demonstrated an improvement in relapse-free survival (the primary endpoint), this difference did not reach statistical significance compared to the placebo group. However, in a prespecified subgroup analysis, gilteritinib showed clear benefit in patients with measurable residual disease (MRD) at the time of transplant. In contrast, patients who had a negative MRD test did not receive significant benefit from gilteritinib.

These findings suggest that maintenance therapy with gilteritinib for up to 24 months may improve relapse-free survival in AML patients who have a FLT3 ITD mutation and are MRD-positive at the time of transplantation.

Summary:

Target:

Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (AML) who have FLT3 internal tandem duplication mutation (FLT3-ITD) AML. These patients are usually routinely treated with FLT3 inhibitors after HCT, but there is limited evidence to support this. Therefore, we conducted a randomized post-HCT maintenance clinical trial with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine whether all of these patients benefit from Or whether detecting measurable residual disease (MRD) could identify those who might benefit.

Methods:

In the first remission, adults with FLT3-ITD AML underwent HSCT and received placebo or gilteritinib 120 mg once daily for 24 months after HSCT. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS) and RFS, and the impact of MRD before and after HSCT on OS.

Result:

Three hundred fifty-six participants were randomized to receive gilteritinib or placebo after HSCT. Although relapse-free survival was higher in the gilteritinib group, the difference was not statistically significant (hazard ratio (HR), 0.679 (95% CI, 0.459 to 1.005); two-sided P = .0518). However, 50.5% of participants had detectable MRD before or after HSCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 (95% CI, 0.316 to 0.838); P = .0065 ). Those without detectable MRD had no benefit (HR, 1.213 (95% CI, 0.616 to 2.387); P = .575).

conclusion:

Although the overall improvement in relapse-free survival was not statistically significant, relapse-free survival was greater for participants with detectable FLT3-ITD MRD before or after HSCT who received treatment with gilteritinib. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HSCT therapy.

Source: Biopress