Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3
05/2024
Journal Article
Authors:
Levis, M. J.;
Hamadani, M.;
Logan, B.;
Jones, R. J.;
Singh, A. K.;
Litzow, M.;
Wingard, J. R.;
Papadopoulos, E. B.;
Perl, A. E.;
Soiffer, R. J.;
Ustun, C.;
Ueda Oshima, M.;
Uy, G. L.;
Waller, E. K.;
Vasu, S.;
Solh, M.;
Mishra, A.;
Muffly, L.;
Kim, H. J.;
Mikesch, J. H.;
Najima, Y.;
Onozawa, M.;
Thomson, K.;
Nagler, A.;
Wei, A. H.;
Marcucci, G.;
Geller, N. L.;
Hasabou, N.;
Delgado, D.;
Rosales, M.;
Hill, J.;
Gill, S. C.;
Nuthethi, R.;
King, D.;
Wittsack, H.;
Mendizabal, A.;
Devine, S. M.;
Horowitz, M. M.;
Chen, Y. B.;
Bmt-Ctn Morpho Study Investigators
Volume:
42
Pagination:
1766-1775
Issue:
15
Journal:
J Clin Oncol
PMID:
38471061
URL:
https://www.ncbi.nlm.nih.gov/pubmed/38471061
Keywords:
Humans *fms-Like Tyrosine Kinase 3/genetics *Leukemia, Myeloid, Acute/genetics/drug therapy/therapy/mortality Male Female Middle Aged *Pyrazines/therapeutic use Adult *Aniline Compounds/therapeutic use
*Hematopoietic Stem Cell Transplantation *Mutation Aged Tandem Repeat Sequences Young Adult Neoplasm, Residual Protein Kinase Inhibitors/therapeutic use Maintenance Chemotherapy Gene Duplication
Abstract:
PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, 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 MRD detectable pre- or post-HCT, 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 showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.
