Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations

作者：Nigel H. Russell, Charlotte S. Wilhelm-Benartzi, Jad Othman, Richard James Dillon, Steven Knapper, Leona M. Batten, Joanna Canham, Emily L. Hinson, Sophie Betteridge, Ulrik Malthe Overgaard, Amanda Gilkes, Nicola E. Potter, Priyanka Mehta, Panagiotis D. Kottaridis, Jamie D. Cavenagh, Claire Jane Hemmaway, Claire Arnold, Sylvie D. Freeman, Mike Dennis, Maria Kallenbach, Marianne Tang Severinsen, Mette Holm, Jan Maxwell Nørgaard, Hans Beier Ommen, Dominic J. Culligan, Jane E. Tighe, Jenny I. O. Craig, Charles R. Crawley, Pramila Krishnamurthy, Walid Sadik, Jeffery Smith, Ranjit Dasgupta, Leanne Berkhan, Peter Bowett, Richard T. Doocey, Shannon Emmett, Timothy E. Hawkins, Nigel W. Patton, Lucy C. Pemberton, Alison Milne, Ashok Roy, Sylwia Simpson, Claire Arnold, Robert J. G. Cuthbert, Damian P. J. Finnegan, Mary Francis McMullin, Victoria Pechey, Richard Lovell, Donald William Milligan, Shankara Paneesha, Paul A Cahalin, Phillipa Kelsey, Sam Ackroyd, Adrian Wiliams, Roger S. Evely, David Ian Marks, Priyanka Mehta, Andrew Fletcher, Maryam Al-Ani, Khalil Ahmed, Richard Lush, Adam Rye, Robert Cutting, Andrew Fletcher, Emma Welch, M.A. Wodzinski, Andrew Butler, Liam Joseph Fernyhough, Peter S. Ganly, Steve Gibbons, Mark B Smith, Ruth L. Spearing, Andy Peniket, Faye Hatcliffe, Amit K. Patel, Kathrine Lindsay, Gillian Brearton, Salah Tuegar, S. Cowley, Adrian Copplestone, Hannah M. Hunter, Patrick G. Medd, Tim Nokes, Simon Rule, Wayne Thomas, Robert Cutting, Joe Joseph, Stuti Kaul, Youssef Sorour, Shingi Chvuka, Hilda Mangos, Annette J. Neylon, Katrina Farrell, Hugh Edwards, Katharine Hanlon, Tom Fail, Margaret Goodrick, Earnest Heartin, Christine F. Hoyle, Adam Rye, Robert A. Carr, Kavita K Raj, Morten Krogh Jensen, Riaz Jan-Mohamed, Richard S. Kaczmarski, Taku Sugai, Debo Ademokun, Isobel Chalmers, A. Hodson, Cesar A. Gomez, S. Sadullah, Mark Kwan, Karyn Longmuir, Isaac Wilson-Morkeh, Ann Hunter, Murray Martin, Kandeepan Saravanamuttu, Gamal Sidra, Sarah S. Burns, Simon DJ Gibbs, Eleni Tholouli, Maadh Aldouri, Vivienne Andrews, Ayed Eden, Moez Dungarwalla, Denise White, Jane Laird, Lindsey Mitchell, John Murphy, Pamela Paterson, Alaeddin Raafat, Deepak Mannari, Simon Davies, Belinda Austen, Sarah L. Allford, Sudhakar Kakalamudi, Supratik Basu, Sunil Hada, Abraham O. Jacob, Alan MacWhonell, Alison M. McCaig, Keith Gelly, Ron Kerr, D. J. Meiklejohn, Sudhir Tauro, Matthew J. Lawes, Angela Bowen, Suchitra Krishnamurthy, Jenny Byrne, Emma P. Das-Gupta, Nigel H. Russell, Simone Stokley, Lone Smidstrup Friis, Claus Werenberg Marcher, Bart Bake, M. Chapple, Paul Moreton, Asad Omran, Kavita Patil, David N.M. Wright, Fergus Jack, Rebecca Maddams, Robert B. Corser, Tanya Cranfield, Helen Dignum, Mary Ganczakowski, Christopher J. Jones, Charles Craddock, Paula Moss, J. A. H. Murray, Claire Jane Hemmaway, Joanne Craig, Peter A. Forsyth, Chris Lush, Ole Wei Bjerrum, Niels Borregaard, Peter Kampmann, Lars Kjeldsen, Ove Juul Nielsen, Carsten Utoft Niemann, Soeren Lykke Petersen, Lene Udby Peter Møller, Arun Alfred, Helen F. Barker, Richard Went, Henri Groch, Stuart Mucklow, Rebecca Sampson, Joseph M. Chacko, Rachel Hall, Renata J. Walewska, Desmond Creach, Bryson Pottinger, Juanah Addada, Malcolm S. Hamilton, Paul M. Kerr, Loretta Ngu, Claudius E. Rudin, Jackie Ruell, Chris Dalley, Harpreet Kaur, John F. Reilly, John Andrew Snowden, Paul Ferguson, Peter Dyer, Deepak Chandra, J. Devos, Elisabeth Grey‐Davies, Louise Hendry, Timothy Corbett, Josephine Crowe, C. Knechtli, Sarah Wexler, Savio Fernandes, Jeff Neilson, John S M Houghton, Simon N. Jowitt, Rowena Thomas-Dewing, Mark Thomas Shaw Williams, Sonya Zaman, Jonathan Cullis, Tamara Everington, Effie Grand, Yasmin Hasan, Richard J. A. Murrin, Farooq Wandoo, Saad Ismail, Unmesh Mohite, Hamdi I. A. Sati, Matthew W. Jenner, Kim Orchard, Deborah K. Richardson, Kayleigh McCloskey, Kate Xu Chin, Neoh Fenella Willis, Amit Sud, Maged I. Gharib, Toby Nicholson, David Bowen, Sarah Janes, Helen Eagleton, A M O'Hea, Jonathan Pattinson, Victoria Hervey, Simon Lyons, Scott R Marshall, Annette Nicolle, Maria Vavyla, Jordan Burgess, Tim C. P. Somervaille, Somerfield Sd, Mohd Mamat, Jo Tomlins, Sana Salesh, Marianna Dávid, Jamie M. Maddox, Diane Plews, Ray Dang, Mike J Potter, Lauren Ellis, Emma Nicholson, Sally Keat, Thubeena M. Ahmed Alhassani, Farahn Anjum, Poulami Chatterjee, Atanas Stanchev, Jayne Peters, Sarah Lindsay-Holmes Srividhya, Senthil S. Chodhouri, Heather E. Eve, Steve Smith, Patrick Roberts, Nicholas Rymes, Rui Zhao New Oo, Kirit M. Ardeshna, Piers A. Blombery, Asim Ijaz Khwaja, David C. Linch, Rakesh Popat, Andres E. Virchis, Kwee Yong, Victoria McIntyre, Gillian A. Horne, Syed Waqas Imam Bokhari, Anton G. Borg, Oliver Chapman, Beth D. Harrison, Nicholas M. Jackson, Shailesh Jobanputra, Mekkali Narayanan, Peter Graham Rose, Hajer Oun, Matthew A. Powell, Julie Gilles, Alison M. Laing, Ian Devanny, Gillian A. Horne, Lea Haskins, Paul Micallef-Eynaud, Peter MacLean, Caroline L. Alvares, Jonathan Kell, Steven Knapper, Kerri A. Davidson, Lorna A. McLintock, Stephen Rogers, Peter M Williamson, Gillian Corbett, Hugh J. B. Goodman, Shahid Islam, Humphrey W. H. Pullon, Peter Johnson, P. Huw Roddie, Elizabeth F. Maughan, Juliet Mills, Salim Shafeek, Santosh Narat, Robin Aitchison, Jonathan Pattinson, Lee R Bond, Laura Munro, David Edwards · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.23.00943 · 被引用次数：47 · 研究领域：Acute Myeloid Leukemia Research、Acute Lymphoblastic Leukemia research、Retinoids in leukemia and cellular processes

PURPOSE To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. PATIENTS AND METHODS One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). RESULTS There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 ( P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the...