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
| Title: | 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 |
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| Authors: | Russell, Nigel H.; Wilhelm-Benartzi, Charlotte; Othman, Jad; Dillon, Richard; Knapper, Steven; Batten, Leona M.; Canham, Joanna; Hinson, Emily L.; Betteridge, Sophie; Overgaard, Ulrik Malthe; Gilkes, Amanda; Potter, Nicola; Mehta, Priyanka; Kottaridis, Panagiotis; Cavenagh, Jamie; Hemmaway, Claire; Arnold, Claire; Freeman, Sylvie D.; Dennis, Mike; Kallenbach, Maria; Severinsen, Marianne; Holm, Mette; Maxwell Norgaard, Jan; Beier Ommen, Hans; Culligan, Dominic; Tighe, Jane; Craig, Jenny; Crawley, Charles; Krishnamurthy, Pramila; Sadik, Walid; Smith, Jeffery; Dasgupta, Ranjit; Berkhan, Leanne; Bowett, Peter; Doocey, Richard; Emmett, Shannon; Hawkins, Timothy; Patton, Nigel; Pemberton, Lucy; Milne, Alison; Roy, Ashok; Simpson, Sylwia; Cuthbert, Robert; Finnegan, Damian; Francis McMullin, Mary; Pechey, Victoria; Lovell, Richard; Milligan, Donald; Paneesha, Shankara; Cahalin, Paul; Kelsey, P.; Ackroyd, Sam; Wiliams, Adrian; Evely, Roger; Marks, David; Fletcher, Andrew; Al-Ani, Maryam; Ahmed, Khalil; Lush, Richard; Rye, Adam; Cutting, Robert; Welch, Emma; Wodzinski, Mark; Butler, Andrew; Fernyhough, Liam; Ganly, Peter; Gibbons, Steve; Smith, Mark; Spearing, Ruth; Peniket, Andy; Hatcliffe, Faye; Patel, Amit; Lindsay, Kathrine; Brearton, Gillian; Tuegar, Salah; Gandhi Anna Cowley, S.; Copplestone, Adrian; Hunter, Hannah; Medd, Patrick; Nokes, Tim; Rule, Simon; Thomas, Wayne; Joseph, Joe; Kaul, Stuti; Sorour, Youssef; Chvuka, Shingi; Mangos, Hilda; Neylon, Annette; Farrell, Katrina; Edwards, Hugh; Hanlon, Katharine; Fail, Tom; Goodrick, Margaret; Heartin, Earnest; Hoyle, Christine; Carr, Robert; Raj, Kavita; Krogh Jensen, Morten; Janmohamed, Riaz; Kaczmarski, Richard; Sugai, Taku; Ademokun, Debo; Chalmers, Isobel; Hodson, Andrew; Gomez, Cesar; Sadullah, Shala; Kwan, Mark; Longmuir, Karyn; Wilson-Morkeh, Isaac; Hunter, Ann; Martin, Murray; Saravanamuttu, Kandeepan; Sidra, Gamal; Burns, Sarah; Gibbs, Simon; Tholouli, Eleni; Aldouri, Maadh; Andrews, Vivienne; Eden, Ayed; Dungarwalla, Moez; White, Denise; Laird, Jane; Mitchell, Lindsey; Murphy, John; Paterson, Pamela; Raafat, Alaeddin; Mannari, Deepak; Davies, Simon; Austen, Belinda; Allford, Sarah; Kakalamudi, Sudhakar; Basu, Supratik; Hada, Sunil; Jacob, Abraham; MacWhonell, Alan; McCaig, Alison; Gelly, Keith; Kerr, Ron; Meiklejohn, David; Tauro, Sudhir; Lawes, Matthew; Bowen, Angela; Krishnamurthy, Suchitra; Byrne, Jenny; Dasgupta, Emma; Russell, Nigel; Stokley, Simone; Friis, Lone; Marcher, Claus; Bake, Bart; Chapple, Mary; Moreton, Paul; Omran, Asad; Patil, Kavita; Wright, David; Jack, Fergus; Maddams, Rebecca; Corser, Robert; Cranfield, Tanya; Dignum, Helen; Ganczakowski, Mary; Jones, Christopher; Craddock, Charles; Moss, Paula; Murray, Jim; Craig, Joanne; Forsyth, Peter; Lush, Chris; Wei Bjerrum, Ole; Borregaard, Niels; Kampmann, Peter; Kjeldsen, Lars; Juul Nielsen, Ove; Niemann, Carsten; Lykke Petersen, Soeren; Udby Peter Møller, Lene; Alfred, Arun; Barker, Helen; Went, Richard; Groch, Henri; Mucklow, Stuart; Sampson, Rebecca; Chacko, Joseph; Hall, Rachel; Walewska, Renata; Creach, Desmond; Pottinger, Bryson; Addada, Juanah (Jo); Hamilton, Malcolm; Kerr, Paul; Ngu, Loretta; Rudin, Claudius; Ruell, Jackie; Dalley, Chris; Kaur, Harpreet; Reilly, John; Snowden, John; Ferguson, Paul; Dyer, Peter; Chandra, Deepak; DeVos, Johannes; Grey-Davies, Elisabeth; Hendry, Louise; Corbett, Timothy; Crowe, Josephine; Knechtli, Christopher; Wexler, Sarah; Fernandes, Savio; Neilson, Jeff; Houghton, John; Jowitt, Simon; Thomas-Dewing, Rowena; Williams, Mark; Zaman, Sonya; Cullis, Jonathan; Everington, Tamara; Grand, Effie; Hasan, Yasmin; Murrin, Richard; Wandoo, Farooq; Ismail, Saad; Mohite, Unmesh; Sati, Hamdi; Jenner, Matthew; Orchard, Kim; Richardson, Deborah; McCloskey, Kayleigh; Xu Chin, Kate; Fenella Willis, Neoh; Sud, Amit; Gharib, Maged; Nicholson, Toby; Bowen, David; Janes, Sarah; Eagleton, Helen; O'Hea, Anne-Marie; Pattinson, Jonathan; Hervey, Victoria; Lyons, Simon; Marshall, Scott; Nicolle, Annette; Vavyla, Maria; Burgess, Jordan; Somervaille, Tim; Somerfield, Sven; Mamat, Mohd; Tomlins, Jo; Salesh, Sana; David, Marianna; Maddox, Jamie; Plews, Diane; Dang, Ray; Potter, Mike; Ellis, Lauren; Nicholson, Emma; Keat, Sally; Ahmed Alhassani, Thubeena M.; Anjum, Farahn; Chatterjee, Poulami; Stanchev, Atanas; Peters, Jayne; Lindsay-Holmes Srividhya, Sarah; Chodhouri, Senthil S.; Eve, Heather; Smith, Steve; Roberts, Patrick; Rymes, Nicholas; Zhao New Oo, Rui; Ardeshna, Kirit; Blombery, Piers; Khwaja, Asim; Linch, David; Popat, Rakesh; Virchis, Andres; Yong, Kwee; McIntyre, Victoria; Horne, Gillian; Bokhari, Syed; Borg, Anton; Chapman, Oliver; Harrison, Beth; Jackson, Nicholas; Jobanputra, Shailesh; Narayanan, Mekkali; Rose, Peter; Oun, Hajer; Powell, Matthew; Gilles, Julie; Laing, Alison; Devanny, Ian; Haskins, Lea; Micallef-Eynaud, Paul; Maclean, Peter; Alvares, Caroline; Kell, Jonathan; Knapper, Steve; Davidson, Kerri; McLintock, Lorna; Rogers, Stephen; Williamson, Peter; Corbett, Gillian; Goodman, Hugh; Islam, Shahid; Pullon, Humphrey; Johnson, Peter; Roddie, P.H.; Maughan, Elizabeth; Mills, Juliet; Shafeek, Salim; Narat, Santosh; Aitchison, Robin; Bond, Lee; Munro, Laura; Edwards, David |
| Publisher Information: | American Society of Clinical Oncology |
| Publication Year: | 2024 |
| Collection: | Cardiff University: ORCA (Online Research @ Cardiff) |
| Description: | PurposeTo determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics.Patients and MethodsOne 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).ResultsThere 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 DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO.ConclusionOverall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| Relation: | https://orca.cardiff.ac.uk/id/eprint/167596/1/russell-et-al-2024-fludarabine-cytarabine-granulocyte-colony-stimulating-factor-and-idarubicin-with-gemtuzumab.pdf; Russell, Nigel H., Wilhelm-Benartzi, Charlotte orcid:0000-0003-4927-6158 orcid:0000-0003-4927-6158, Othman, Jad, Dillon, Richard, Knapper, Steven https://orca.cardiff.ac.uk/view/cardiffauthors/A016111L.html orcid:0000-0002-6405-4441 orcid:0000-0002-6405-4441, Batten, Leona M. https://orca.cardiff.ac.uk/view/cardiffauthors/A2425663S.html, Canham, Joanna https://orca.cardiff.ac.uk/view/cardiffauthors/A038537L.html orcid:0000-0003-3482-0990 orcid:0000-0003-3482-0990, Hinson, Emily L., Betteridge, Sophie, Overgaard, Ulrik Malthe, Gilkes, Amanda https://orca.cardiff.ac.uk/view/cardiffauthors/A062527N.html, Potter, Nicola, Mehta, Priyanka, Kottaridis, Panagiotis, Cavenagh, Jamie, Hemmaway, Claire, Arnold, Claire, Freeman, Sylvie D., Dennis, Mike, Kallenbach, Maria, Severinsen, Marianne, Holm, Mette, Maxwell Norgaard, Jan, Beier Ommen, Hans, Culligan, Dominic, Tighe, Jane, Craig, Jenny, Crawley, Charles, Krishnamurthy, Pramila, Sadik, Walid, Smith, Jeffery, Dasgupta, Ranjit, Berkhan, Leanne, Bowett, Peter, Doocey, Richard, Emmett, Shannon, Hawkins, Timothy, Patton, Nigel, Pemberton, Lucy, Milne, Alison, Roy, Ashok, Simpson, Sylwia, Arnold, Claire, Cuthbert, Robert, Finnegan, Damian, Francis McMullin, Mary, Pechey, Victoria, Lovell, Richard, Milligan, Donald, Paneesha, Shankara, Cahalin, Paul, Kelsey, P., Ackroyd, Sam, Wiliams, Adrian, Evely, Roger, Marks, David, Mehta, Priyanka, Fletcher, Andrew, Al-Ani, Maryam, Ahmed, Khalil, Lush, Richard, Rye, Adam, Cutting, Robert, Fletcher, Andrew, Welch, Emma, Wodzinski, Mark, Butler, Andrew, Fernyhough, Liam, Ganly, Peter, Gibbons, Steve, Smith, Mark, Spearing, Ruth, Peniket, Andy, Hatcliffe, Faye, Patel, Amit, Lindsay, Kathrine, Brearton, Gillian, Tuegar, Salah, Gandhi Anna Cowley, S., Copplestone, Adrian, Hunter, Hannah, Medd, Patrick, Nokes, Tim, Rule, Simon, Thomas, Wayne, Cutting, Robert, Joseph, Joe, Kaul, Stuti, Sorour, Youssef, Chvuka, Shingi, Mangos, Hilda, Neylon, Annette, Farrell, Katrina, Edwards, Hugh, Hanlon, Katharine, Fail, Tom, Goodrick, Margaret, Heartin, Earnest, Hoyle, Christine, Rye, Adam, Carr, Robert, Raj, Kavita, Krogh Jensen, Morten, Janmohamed, Riaz, Kaczmarski, Richard, Sugai, Taku, Ademokun, Debo, Chalmers, Isobel, Hodson, Andrew, Gomez, Cesar, Sadullah, Shala, Kwan, Mark, Longmuir, Karyn, Wilson-Morkeh, Isaac, Hunter, Ann, Martin, Murray, Saravanamuttu, Kandeepan, Sidra, Gamal, Burns, Sarah, Gibbs, Simon, Tholouli, Eleni, Aldouri, Maadh, Andrews, Vivienne, Eden, Ayed, Dungarwalla, Moez, White, Denise, Laird, Jane, Mitchell, Lindsey, Murphy, John, Paterson, Pamela, Raafat, Alaeddin, Mannari, Deepak, Davies, Simon, Austen, Belinda, Allford, Sarah, Kakalamudi, Sudhakar, Basu, Supratik, Hada, Sunil, Jacob, Abraham, MacWhonell, Alan, McCaig, Alison, Gelly, Keith, Kerr, Ron, Meiklejohn, David, Tauro, Sudhir, Lawes, Matthew, Bowen, Angela, Krishnamurthy, Suchitra, Byrne, Jenny, Dasgupta, Emma, Russell, Nigel, Stokley, Simone, Friis, Lone, Marcher, Claus, Bake, Bart, Chapple, Mary, Moreton, Paul, Omran, Asad, Patil, Kavita, Wright, David, Jack, Fergus, Maddams, Rebecca, Corser, Robert, Cranfield, Tanya, Dignum, Helen, Ganczakowski, Mary, Jones, Christopher, Craddock, Charles, Moss, Paula, Murray, Jim, Hemmaway, Claire, Craig, Joanne, Forsyth, Peter, Lush, Chris, Wei Bjerrum, Ole, Borregaard, Niels, Kampmann, Peter, Kjeldsen, Lars, Juul Nielsen, Ove, Niemann, Carsten, Lykke Petersen, Soeren, Udby Peter Møller, Lene, Alfred, Arun, Barker, Helen, Went, Richard, Groch, Henri, Mucklow, Stuart, Sampson, Rebecca, Chacko, Joseph, Hall, Rachel, Walewska, Renata, Creach, Desmond, Pottinger, Bryson, Addada, Juanah (Jo), Hamilton, Malcolm, Kerr, Paul, Ngu, Loretta, Rudin, Claudius, Ruell, Jackie, Dalley, Chris, Kaur, Harpreet, Reilly, John, Snowden, John, Ferguson, Paul, Dyer, Peter, Chandra, Deepak, DeVos, Johannes, Grey-Davies, Elisabeth, Hendry, Louise, Corbett, Timothy, Crowe, Josephine, Knechtli, Christopher, Wexler, Sarah, Fernandes, Savio, Neilson, Jeff, Houghton, John, Jowitt, Simon, Thomas-Dewing, Rowena, Williams, Mark, Zaman, Sonya, Cullis, Jonathan, Everington, Tamara, Grand, Effie, Hasan, Yasmin, Murrin, Richard, Wandoo, Farooq, Ismail, Saad, Mohite, Unmesh, Sati, Hamdi, Jenner, Matthew, Orchard, Kim, Richardson, Deborah, McCloskey, Kayleigh, Xu Chin, Kate, Fenella Willis, Neoh, Sud, Amit, Gharib, Maged, Nicholson, Toby, Bowen, David, Janes, Sarah, Eagleton, Helen, O'Hea, Anne-Marie, Pattinson, Jonathan, Hervey, Victoria, Lyons, Simon, Marshall, Scott, Nicolle, Annette, Vavyla, Maria, Burgess, Jordan, Somervaille, Tim, Somerfield, Sven, Mamat, Mohd, Tomlins, Jo, Salesh, Sana, David, Marianna, Maddox, Jamie, Plews, Diane, Dang, Ray, Potter, Mike, Ellis, Lauren, Nicholson, Emma, Keat, Sally, Ahmed Alhassani, Thubeena M., Anjum, Farahn, Chatterjee, Poulami, Stanchev, Atanas, Peters, Jayne, Lindsay-Holmes Srividhya, Sarah, Chodhouri, Senthil S., Eve, Heather, Smith, Steve, Roberts, Patrick, Rymes, Nicholas, Zhao New Oo, Rui, Ardeshna, Kirit, Blombery, Piers, Khwaja, Asim, Linch, David, Popat, Rakesh, Virchis, Andres, Yong, Kwee, McIntyre, Victoria, Horne, Gillian, Bokhari, Syed, Borg, Anton, Chapman, Oliver, Harrison, Beth, Jackson, Nicholas, Jobanputra, Shailesh, Narayanan, Mekkali, Rose, Peter, Oun, Hajer, Powell, Matthew, Gilles, Julie, Laing, Alison, Devanny, Ian, Horne, Gillian, Haskins, Lea, Micallef-Eynaud, Paul, Maclean, Peter, Alvares, Caroline, Kell, Jonathan, Knapper, Steve, Davidson, Kerri, McLintock, Lorna, Rogers, Stephen, Williamson, Peter, Corbett, Gillian, Goodman, Hugh, Islam, Shahid, Pullon, Humphrey, Johnson, Peter, Roddie, P.H., Maughan, Elizabeth, Mills, Juliet, Shafeek, Salim, Narat, Santosh, Aitchison, Robin, Pattinson, Jonathan, Bond, Lee, Munro, Laura and Edwards, David 2024. 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. Journal of Clinical Oncology 42 (10) , pp. 1158-1168. 10.1200/JCO.23.00943 https://doi.org/10.1200/JCO.23.00943 file https://orca.cardiff.ac.uk/id/eprint/167596/1/russell-et-al-2024-fludarabine-cytarabine-granulocyte-colony-stimulating-factor-and-idarubicin-with-gemtuzumab.pdf |
| DOI: | 10.1200/JCO.23.00943 |
| Availability: | https://orca.cardiff.ac.uk/id/eprint/167596/; https://doi.org/10.1200/JCO.23.00943 |
| Rights: | cc_by_nc_nd_4_0 |
| Accession Number: | edsbas.9891DFA4 |
| Database: | BASE |