Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML
- Author(s)
- Levis, MJ; Oshima, MU; Hamadani, M; Solh, M; Logan, BR; Muffly, LS; Jones, RJ; Thomson, K; Singh, AK; Hill, J; Litzow, MR; Mendizabal, A; Wingard, JR; Papadopoulos, EB; Perl, AE; Soiffer, RJ; Ustun, C; Uy, GL; Waller, EK; Vasu, S; Mishra, A; Kim, HJ; Stelljes, M; Najima, Y; Onozawa, M; Nagler, A; Wei, AH; Marcucci, G; Chen, C; Hasabou, N; Rosales, M; Gill, SC; Nuthethi, R; King, D; Devine, SM; Horowitz, MM; Chen, YB;
- Details
- Publication Year 2025-05-08,Volume 145,Issue #19,Page 2138-2148
- Journal Title
- Blood
- Publication Type
- Research article
- Abstract
- BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 ("MORPHO") was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively affected RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared with 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild-type clones (assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multiclonal disease. These data demonstrate the potential of FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML. This trial was registered at www.clinicaltrials.gov as #NCT02997202.
- Publisher
- American Society of Hematology
- Keywords
- Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; *Aniline Compounds/therapeutic use/administration & dosage; *fms-Like Tyrosine Kinase 3/genetics; *Hematopoietic Stem Cell Transplantation; *Leukemia, Myeloid, Acute/genetics/mortality/pathology/therapy; *Mutation; Neoplasm, Residual; *Pyrazines/therapeutic use/administration & dosage
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1182/blood.2024025154
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-21 06:44:59
Last Modified: 2025-06-02 07:40:45