Regional practice differences significantly impact benefit from post-HCT gilteritinib for FLT3-ITD AML

BMT CTN 1506 ("MORPHO") was a phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib versus placebo for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) in first remission. Subgroup analysis indicated a significant benefit of post-HCT gilteritinib for participants in North America, but no benefit for those in Europe or Asia. We conducted a post-hoc analysis of the data focusing on days from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD measurable residual disease (MRD). Participants transplanted < 120 days from AML diagnosis and/or those treated with FLT3 inhibition pre-HCT were more likely to have improved survival from post-HCT gilteritinib. Pre-HCT MRD levels were higher (P = 0.001) in participants transplanted within 120 days from diagnosis and in those treated with a FLT3 inhibitor pre-HCT and transplanted within 120 days (P = 0.008). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, as participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Time from AML diagnosis to HCT and pre-HCT FLT3 inhibitor use both appeared to impact MRD levels immediately prior to HCT, and geographic differences in these two practice patterns likely accounted for the observed regional differences in benefit from post-HCT gilteritinib. Increasing the number of courses of treatment pre-HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition, but with a presumed risk of some patients experiencing early progression. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

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Journal
Blood Advances
Published
2026-07-30
DOI
https://doi.org/10.1182/bloodadvances.2026020327
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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article

Regional practice differences significantly impact benefit from post-HCT gilteritinib for FLT3-ITD AML

John R. Wingard, Lori S. Muffly, Melhem Solh, Steven M. Devine et al.
Blood Advances
Acute Myeloid Leukemia Research
article

Regional practice differences significantly impact benefit from post-HCT gilteritinib for FLT3-ITD AML

John R. Wingard, Lori S. Muffly, Melhem Solh, Steven M. Devine, Mehdi Hamadani, Edmund K. Waller, Nahla Hasabou, Caroline Chen, Denise King, Yi‐Bin Chen, Rishita Nuthethi, Alexander E. Perl, Masahiro Onozawa, Esperanza B. Papadopoulos, Jason E. Hill, Adam Mendizabal, Celalettin Üstün, Yuho Najima, Stanley C. Gill, Asmita Mishra, Mark Robert Litzow, Mark J. Levis, Geoffrey L. Uy, Hee‐Je Kim, Masumi Ueda, Kirsty Thomson, Matt Rosales, Robert J. Soiffer, Richard J. Jones, Mary M Horowitz, Sumithira Vasu, Brent R Logan, Matthias Stelljes, Anurag K Singh
article en

Abstract

BMT CTN 1506 ("MORPHO") was a phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib versus placebo for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) in first remission. Subgroup analysis indicated a significant benefit of post-HCT gilteritinib for participants in North America, but no benefit for those in Europe or Asia. We conducted a post-hoc analysis of the data focusing on days from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD measurable residual disease (MRD). Participants transplanted < 120 days from AML diagnosis and/or those treated with FLT3 inhibition pre-HCT were more likely to have improved survival from post-HCT gilteritinib. Pre-HCT MRD levels were higher (P = 0.001) in participants transplanted within 120 days from diagnosis and in those treated with a FLT3 inhibitor pre-HCT and transplanted within 120 days (P = 0.008). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, as participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Time from AML diagnosis to HCT and pre-HCT FLT3 inhibitor use both appeared to impact MRD levels immediately prior to HCT, and geographic differences in these two practice patterns likely accounted for the observed regional differences in benefit from post-HCT gilteritinib. Increasing the number of courses of treatment pre-HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition, but with a presumed risk of some patients experiencing early progression. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Blood Advances
Northside Hospital (US), University College Hospital (GB), National Marrow Donor Program (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Johns Hopkins University (US), Emory University (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), Moffitt Cancer Center (US), Tokyo Metropolitan Komagome Hospital (JP), University of Florida (US), Fred Hutch Cancer Center (US), University Hospital Münster (DE), Emmes (United States) (US), Dana-Farber Cancer Institute (US), University of Kansas Medical Center (US), Global Cancer Institute (US), Hokkaido University Hospital (JP), The Catholic University of Korea Seoul St. Mary's Hospital (KR), Sidney Kimmel Comprehensive Cancer Center (US), Astellas Pharma (United States) (US), University College London (GB), Rush University (US), The Ohio State University (US), University of Pennsylvania (US), Catholic University of Korea (KR), Florida College (US), Stanford University (US)
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Acute Myeloid Leukemia Research
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