Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of <i>FLT3</i>
Mark J. Levis, Mehdi Hamadani, Brent R. Logan, Richard J. Jones, Anurag K. Singh, Mark R. Litzow, John R. Wingard, Esperanza B. Papadopoulos, Alexander E. Perl, Robert J. Soiffer, Celalettin Üstün, Masumi Ueda, Geoffrey L. Uy, Edmund K. Waller, Sumithra Vasu, Melhem Solh, Asmita Mishra, Lori Muffly, Hee‐Je Kim, Jan‐Henrik Mikesch, Yuho Najima, Masahiro Onozawa, Kirsty Thomson, Arnon Nagler, Andrew H. Wei, Guido Marcucci, Nancy L. Geller, Nahla Hasabou, David Delgado, Matt Rosales, Jason E. Hill, Stanley C. Gill, Rishita Nuthethi, Denise King, Heather Wittsack, Adam Mendizabal, Steven M. Devine, Mary M. Horowitz, Yi‐Bin Chen, on behalf of the BMT-CTN 1506/MORPHO Study Investigators, Ed Agura, Jessica K. Altman, Achiles Anagnostopoulos, Sarah Anand, Andrew Artz, Walter E. Aulitzky, Sophia Balderman, Karen K. Ballen, Michael W. Becker, Yves Béguin, Leanne Berkahn, Zwi Berneman, Vijaya Raj Bhatt, Ian Bilmon, Francesca Bonifazi, Adrienne Briggs, Benedetto Bruno, Claudio G. Brunstein, Michael Byrne, Jenny Byrne, Mónica Cabrero, Roberto Cairoli, George Carrum, Jan Černý, Yi‐Bin Chen, June‐Won Cheong, Fabio Ciceri, Mercedes Colorado, Rachel J. Cook, Daniel R. Couriel, Charles Craddock, Lloyd E. Damon, Abhinav Deol, Yohan Desbrosses, Steve Devine, Carmela Di Grazia, Antonio Di Stasi, Ajoy Dias, Kathy Dorritie, James Essell, Tetsuya Eto, Sherif S. Farag, Édouard Forcade, Olga Frankfurt, Shin‐ichiro Fujiwara, Takahiro Fukuda, Kentaro Fukushima, Sabine Fürst, Tatsunori Goto, Aric C. Hall, Shunsuke Hatta, Yosr Hicheri, Mitchell E. Horwitz, Hsin‐An Hou, Jonathan How, Dianna S. Howard, Wei‐Hsun Hsu, Anne Huynh, David Irvine, Takayuki Ishikawa
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.