Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3

Levis, MJ; HILL, J; Hamadani, M; Logan, B; Jones, RJ; Singh, AK; Litzow, M; Wingard, JR; Papadopoulos, EB; Perl, AE; Soiffer, RJ; Ustun, C; Ueda Oshima, M; Uy, GL; Waller, EK; Vasu, S; Solh, M; Mishra, A; Muffly, L; Kim, HJ; Mikesch, JH; Najima, Y; Onozawa, M; Thomson, K; Nagler, A; Wei, AH; Marcucci, G; Geller, NL; Hasabou, N; Delgado, D; Rosales, M; Gill, SC; Nuthethi, R; King, D; Wittsack, H; Mendizabal, A; Devine, SM; Horowitz, MM; Chen, YB

Author(s): Levis, MJ; HILL, J; Hamadani, M; Logan, B; Jones, RJ; Singh, AK; Litzow, M; Wingard, JR; Papadopoulos, EB; Perl, AE; Soiffer, RJ; Ustun, C; Ueda Oshima, M; Uy, GL; Waller, EK; Vasu, S; Solh, M; Mishra, A; Muffly, L; Kim, HJ; Mikesch, JH; Najima, Y; Onozawa, M; Thomson, K; Nagler, A; Wei, AH; Marcucci, G; Geller, NL; Hasabou, N; Delgado, D; Rosales, M; Gill, SC; Nuthethi, R; King, D; Wittsack, H; Mendizabal, A; Devine, SM; Horowitz, MM; Chen, YB;
Details: Publication Year 2024-03-12,Volume 42,Issue #15,Page 1766-1775
Journal Title: Journal of Clinical Oncology
Abstract: PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (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.
Publisher: ASCO
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
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 38471061
Publisher's Version: https://doi.org/10.1200/jco.23.02474
Open Access at Publisher's Site: https://doi.org/10.1200/JCO.23.02474
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: levis-et-al-2024-gilteritinib-as-post-transplant-maintenance-for-aml-with-internal-tandem-duplication-mutation-of-flt3.pdf - (1.29MB, application/pdf)

Creation Date: 2024-03-18 02:11:32

Last Modified: 2024-07-26 09:36:41