AML-065: Measurable Residual Disease Status and FLT3 Inhibitor Therapy in Patients with FLT3-ITD-Mutated AML Following Allogeneic Hematopoietic Cell Transplantation

Abstract

<h3>Context:</h3> In 2019, our transplant program initiated prospective <i>FLT3-ITD</i> measurable residual disease (MRD) monitoring by next-generation sequencing (NGS) of the peripheral blood or bone marrow throughout the first three months following HCT for all patients with FLT3-ITD-mutated AML undergoing HCT. We encouraged FLT3 inhibitor use as post-HCT maintenance. <h3>Objective:</h3> To evaluate the impact of post-HCT FLT3 MRD testing and FLT3 inhibitor use in a non-clinical trial setting. <h3>Design:</h3> Observational study of adults with FLT3-ITD-mutated AML who underwent allogeneic HCT at Stanford University between April 2019 and August 2020. <h3>Setting:</h3> Tertiary referral center. <h3>Patients or Other Participants:</h3> Thirty-six adults with FLT3-ITD-mutated AML are included in this study. Two patients were excluded from analyses due to early graft failure and receipt of azacitidine/enasidenib maintenance therapy. <h3>Interventions:</h3> Twenty-four patients (71%) received an FLT3 inhibitor after HCT, initiated a median of 2.8 months after transplant (range: 0.7–17.1). The median duration was 6.8 months (range: 1.1–18.8). <h3>Main Outcome Measures:</h3> Progression-free survival (PFS) and overall survival (OS). <h3>Results:</h3> Ten patients (29%) had detectable MRD within the first three months following HCT, while 24 (71%) patients remained MRD-negative. Although there was a trend toward inferior PFS for patients with early post-HCT MRD (p = 0.12), OS was not significantly impacted by MRD (p = 0.66). FLT3 inhibitor therapy improved PFS and OS, particularly in MRD-negative patients (maintenance <i>vs</i> no maintenance: PFS not reached <i>vs</i> 5.52 months, p=0.002; OS not reached <i>vs</i> 5.85 months, p=0.006). <h3>Conclusions:</h3> Clinical relapse can be prevented, even in patients with post-HCT MRD, by using early FLT3 inhibitor maintenance therapy, in keeping with the results from the SORMAIN trial. Real-time sensitive MRD testing allows clinicians to begin early initiation of FLT3 inhibitor therapy. This work was partially supported by the National Institutes of Health Grant UL1-TR003142 and Grant P30-CA124435.