Gilteritinib as post-transplant maintenance for AML with internal tandem duplication mutation of FLT3 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.; on behalf of the BMT-CTN 1506/MORPHO Study Investigators |
| Article Title: | Gilteritinib as post-transplant maintenance for AML with internal tandem duplication mutation of FLT3 |
| Abstract: | PURPOSEAllogeneic 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.METHODSAdults 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.RESULTSThree 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).CONCLUSIONAlthough 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. © American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; controlled study; aged; middle aged; young adult; gene mutation; major clinical study; overall survival; genetics; mutation; leukemia, myeloid, acute; clinical trial; mortality; neutropenia; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; methotrexate; follow up; infection; neutrophil count; pyrazines; anemia; bone marrow suppression; protein kinase inhibitor; leukopenia; randomized controlled trial; thrombocytopenia; gene frequency; hematopoietic stem cell transplantation; cancer mortality; alanine aminotransferase blood level; aspartate aminotransferase blood level; protein kinase inhibitors; alanine aminotransferase; aspartate aminotransferase; acute graft versus host disease; chronic graft versus host disease; myeloablative conditioning; minimal residual disease; neoplasm, residual; multicenter study; graft versus host reaction; reduced intensity conditioning; gene duplication; allogeneic hematopoietic stem cell transplantation; creatine kinase; leukocyte count; aniline compounds; calcineurin inhibitor; leukemia relapse; double blind procedure; pyrazine derivative; fluconazole; posaconazole; voriconazole; platelet count; itraconazole; creatine kinase blood level; leukemia remission; recurrence free survival; cumulative incidence; tandem repeat sequences; cd135 antigen; tandem repeat; acute myeloid leukemia; aniline derivative; fms-like tyrosine kinase 3; maintenance chemotherapy; mycophenolate mofetil; intention to treat analysis; humans; human; male; female; article; treatment interruption; gilteritinib; isavuconazonium |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 42 |
| Issue: | 15 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-05-20 |
| Start Page: | 1766 |
| End Page: | 1775 |
| Language: | English |
| DOI: | 10.1200/jco.23.02474 |
| PUBMED: | 38471061 |
| PROVIDER: | scopus |
| PMCID: | PMC11095884 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
