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