Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3
Authors: Levis Mark J. , Hamadani Mehdi , Logan Brent , Jones Richard J. , Singh Anurag K. , Litzow Mark , Wingard John R. , Papadopoulos Esperanza B. , Perl Alexander E. , Soiffer Robert J. , Ustun Celalettin , Ueda Oshima Masumi , Uy Geoffrey L. , Waller Edmund K. , Vasu Sumithra , Solh Melhem , Mishra Asmita , Muffly Lori , Kim Hee-Je , Mikesch Jan-Henrik , Najima Yuho , Onozawa Masahiro , Thomson Kirsty , Nagler Arnon , Wei Andrew H. , Marcucci Guido , Geller Nancy L. , Hasabou Nahla , Delgado David , Rosales Matt , Hill Jason , Gill Stanley C. , Nuthethi Rishita , King Denise , Wittsack Heather , Mendizabal Adam , Devine Steven M. , Horowitz Mary M. , Chen Yi-Bin ,   on behalf of the BMT-CTN 1506/MORPHO Study Investigators, Agura Ed , Altman Jessica , Anagnostopoulos Achiles , Anand Sarah , Artz Andrew , Aulitzky Walter , Balderman Sophia , Ballen Karen , Becker Michael , Beguin Yves , Berkahn Leanne , Berneman Zwi , Bhatt Vijaya , Bilmon Ian , Bonifazi Francesca , Briggs Adrienne , Bruno Benedetto , Brunstein Claudio , Byrne Michael , Byrne Jenny , Cabrero Monica , Cairoli Roberto , Carrum George , Cerny Jan , Chen Yi-Bin , Cheong June-Won , Ciceri Fabio , Colorado Mercedes , Cook Rachel , Couriel Daniel , Craddock Charles , Damon Lloyd , Deol Abhinav , Desbrosses Yohan , Devine Steve , Di Grazia Carmela , Di Stasi Antonio , Dias Ajoy , Dorritie Kathy , Essell James , Eto Tetsuya , Farag Sherif , Forcade Edouard , Frankfurt Olga , Fujiwara Shinichiro , Fukuda Takahiro , Fukushima Kentaro , Furst Sabine , Goto Tatsunori , Hall Aric , Hatta Shunsuke , Hicheri Yosr , Horwitz Mitchell , Hou Hsin-An , How Jonathan , Howard Dianna , Hsu Wei-Hsun (Blake) , Huynh Anne , Irvine David , Ishikawa Takayuki , Jamieson Katarzyna , Jedrzejczak Wieslaw , Jethava Yogesh , Jimenez Antonio , Jung Chul Won , Kanda Junya , Karakasis Dimitrios , Kato Jun , Kekre Natasha , Khera Nandita , Kim Hee-Je , Klein Andreas , Kobbe Guido , Kornblit Brian , Kota Vamsi , Lachance Silvy , Leber Brian , Lee Catherine , Lee Je Hwan , Levis Mark J. , Lin Tung-Liang , Litzow Mark , Liu Ta-Chih , Martelli Maurizio , Martinez Carmen , Matsuoka Kenichi , McCarty John , Mendez Lourdes , Michelis Fotios , Mikesch Jan-Henrik , Mineishi Shin , Mishra Asmita , Mohty Mohamad , Moors Ine , Motyckova Gabriela , Mueller Lutz , Muffly Lori , Najima Yuho , Nakamae Hirohisa , Nakano Nobuaki , Nathan Sunita , Nicholson Emma , Norkin Maxim , Ogawa Yoshiaki , Olesen Gitte , Oluwole Olalekan , Onozawa Masahiro , Pantin Jeremy , Papadopoulos Esperanza B. , Paulson Kristjan , Pemberton Lucy , Perera Travis , Perl Alexander E. , Piatkowska-Jakubas Beata , Poire Xavier , Protheroe Rachel , Rambaldi Alessandro , Ritchie David , Ross Kelly , Rubio Marie-Therese , Santarone Stella , Sanz Caballer Jaime , Sawa Masashi , Schaar Dale , Scheid Christoph , Schriber Jeffrey , Seropian Stuart , Shah Nilay , Shah Nirav , Shore Tsiporah , Gil Jorge Sierra , Singh Anurag , Sobecks Ronald , Socie Gerard , Soiffer Robert , Solh Melhem , Sprague Kellie , Spyridonidis Alexandros , Stelljes Matthias , Stiff Patrick , Stuart Robert , Tanaka Masatsugu , Tandra Anand , Tholouli Eleni , Thomas Xavier , Thomson Kirsty , Tiribelli Mario , Tomlinson Benjamin , Tsirigotis Panagiotis , Tzachanis Dimitrios , Uchida Naoyuki , Ueda Masumi , Ustun Celalettin , Uy Geoffrey L. , Valcarcel Ferreiras David , Vasu Sumithra , Wagner Eva , Waller Edmund K. , Watson Anne-Marie , Weisdorf Daniel , Wingard John R. , Wolschke Christine , Wrobel Tomasz , Yakoub-Agha Ibrahim , Yamauchi Takuji , Yared Jean , Yeh Su-Peng , Yoon Sung-Soo , Yoshihara Satoshi 
Published: March 2024

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.