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
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 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.
CONCLUSION: Overall, 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
|---|---|
| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 42(2024), 10 vom: 01. März, Seite 1158-1168 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Russell, Nigel H [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic ClinicalTrials.gov: ISRCTN78449203 Citation Status MEDLINE |
|---|
| doi: |
10.1200/JCO.23.00943 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367059118 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367059118 | ||
| 003 | DE-627 | ||
| 005 | 20240330000745.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240114s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1200/JCO.23.00943 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1355.xml |
| 035 | |a (DE-627)NLM367059118 | ||
| 035 | |a (NLM)38215358 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Russell, Nigel H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.03.2024 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: ISRCTN78449203 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics | ||
| 520 | |a 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) | ||
| 520 | |a 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 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 | ||
| 520 | |a CONCLUSION: Overall, 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Idarubicin |2 NLM | |
| 650 | 7 | |a ZRP63D75JW |2 NLM | |
| 650 | 7 | |a Gemtuzumab |2 NLM | |
| 650 | 7 | |a 93NS566KF7 |2 NLM | |
| 650 | 7 | |a Granulocyte Colony-Stimulating Factor |2 NLM | |
| 650 | 7 | |a 143011-72-7 |2 NLM | |
| 650 | 7 | |a Cytarabine |2 NLM | |
| 650 | 7 | |a 04079A1RDZ |2 NLM | |
| 650 | 7 | |a fludarabine |2 NLM | |
| 650 | 7 | |a P2K93U8740 |2 NLM | |
| 650 | 7 | |a Vidarabine |2 NLM | |
| 650 | 7 | |a FA2DM6879K |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Core Binding Factors |2 NLM | |
| 650 | 7 | |a FLT3 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a fms-Like Tyrosine Kinase 3 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Wilhelm-Benartzi, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Othman, Jad |e verfasserin |4 aut | |
| 700 | 1 | |a Dillon, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Knapper, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Batten, Leona M |e verfasserin |4 aut | |
| 700 | 1 | |a Canham, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Hinson, Emily L |e verfasserin |4 aut | |
| 700 | 1 | |a Betteridge, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Overgaard, Ulrik Malthe |e verfasserin |4 aut | |
| 700 | 1 | |a Gilkes, Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Potter, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Priyanka |e verfasserin |4 aut | |
| 700 | 1 | |a Kottaridis, Panagiotis |e verfasserin |4 aut | |
| 700 | 1 | |a Cavenagh, Jamie |e verfasserin |4 aut | |
| 700 | 1 | |a Hemmaway, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Arnold, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Freeman, Sylvie D |e verfasserin |4 aut | |
| 700 | 1 | |a Dennis, Mike |e verfasserin |4 aut | |
| 700 | 0 | |a PORTEC Study Group |e verfasserin |4 aut | |
| 700 | 1 | |a Kallenbach, Maria |e investigator |4 oth | |
| 700 | 1 | |a Severinsen, Marianne |e investigator |4 oth | |
| 700 | 1 | |a Holm, Mette |e investigator |4 oth | |
| 700 | 1 | |a Maxwell Norgaard, Jan |e investigator |4 oth | |
| 700 | 1 | |a Beier Ommen, Hans |e investigator |4 oth | |
| 700 | 1 | |a Culligan, Dominic |e investigator |4 oth | |
| 700 | 1 | |a Tighe, Jane |e investigator |4 oth | |
| 700 | 1 | |a Craig, Jenny |e investigator |4 oth | |
| 700 | 1 | |a Crawley, Charles |e investigator |4 oth | |
| 700 | 1 | |a Krishnamurthy, Pramila |e investigator |4 oth | |
| 700 | 1 | |a Sadik, Walid |e investigator |4 oth | |
| 700 | 1 | |a Smith, Jeffery |e investigator |4 oth | |
| 700 | 1 | |a Dasgupta, Ranjit |e investigator |4 oth | |
| 700 | 1 | |a Berkhan, Leanne |e investigator |4 oth | |
| 700 | 1 | |a Bowett, Peter |e investigator |4 oth | |
| 700 | 1 | |a Doocey, Richard |e investigator |4 oth | |
| 700 | 1 | |a Emmett, Shannon |e investigator |4 oth | |
| 700 | 1 | |a Hawkins, Timothy |e investigator |4 oth | |
| 700 | 1 | |a Patton, Nigel |e investigator |4 oth | |
| 700 | 1 | |a Pemberton, Lucy |e investigator |4 oth | |
| 700 | 1 | |a Milne, Alison |e investigator |4 oth | |
| 700 | 1 | |a Roy, Ashok |e investigator |4 oth | |
| 700 | 1 | |a Simpson, Sylwia |e investigator |4 oth | |
| 700 | 1 | |a Arnold, Claire |e investigator |4 oth | |
| 700 | 1 | |a Cuthbert, Robert |e investigator |4 oth | |
| 700 | 1 | |a Finnegan, Damian |e investigator |4 oth | |
| 700 | 1 | |a Francis McMullin, Mary |e investigator |4 oth | |
| 700 | 1 | |a Pechey, Victoria |e investigator |4 oth | |
| 700 | 1 | |a Lovell, Richard |e investigator |4 oth | |
| 700 | 1 | |a Milligan, Donald |e investigator |4 oth | |
| 700 | 1 | |a Paneesha, Shankara |e investigator |4 oth | |
| 700 | 1 | |a Cahalin, Paul |e investigator |4 oth | |
| 700 | 1 | |a Kelsey, P |e investigator |4 oth | |
| 700 | 1 | |a Ackroyd, Sam |e investigator |4 oth | |
| 700 | 1 | |a Wiliams, Adrian |e investigator |4 oth | |
| 700 | 1 | |a Evely, Roger |e investigator |4 oth | |
| 700 | 1 | |a Marks, David |e investigator |4 oth | |
| 700 | 1 | |a Mehta, Priyanka |e investigator |4 oth | |
| 700 | 1 | |a Fletcher, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Al-Ani, Maryam |e investigator |4 oth | |
| 700 | 1 | |a Ahmed, Khalil |e investigator |4 oth | |
| 700 | 1 | |a Lush, Richard |e investigator |4 oth | |
| 700 | 1 | |a Rye, Adam |e investigator |4 oth | |
| 700 | 1 | |a Cutting, Robert |e investigator |4 oth | |
| 700 | 1 | |a Fletcher, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Welch, Emma |e investigator |4 oth | |
| 700 | 1 | |a Wodzinski, Mark |e investigator |4 oth | |
| 700 | 1 | |a Butler, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Fernyhough, Liam |e investigator |4 oth | |
| 700 | 1 | |a Ganly, Peter |e investigator |4 oth | |
| 700 | 1 | |a Gibbons, Steve |e investigator |4 oth | |
| 700 | 1 | |a Smith, Mark |e investigator |4 oth | |
| 700 | 1 | |a Spearing, Ruth |e investigator |4 oth | |
| 700 | 1 | |a Peniket, Andy |e investigator |4 oth | |
| 700 | 1 | |a Hatcliffe, Faye |e investigator |4 oth | |
| 700 | 1 | |a Patel, Amit |e investigator |4 oth | |
| 700 | 1 | |a Lindsay, Kathrine |e investigator |4 oth | |
| 700 | 1 | |a Brearton, Gillian |e investigator |4 oth | |
| 700 | 1 | |a Tuegar, Salah |e investigator |4 oth | |
| 700 | 1 | |a Gandhi Anna Cowley, S |e investigator |4 oth | |
| 700 | 1 | |a Copplestone, Adrian |e investigator |4 oth | |
| 700 | 1 | |a Hunter, Hannah |e investigator |4 oth | |
| 700 | 1 | |a Medd, Patrick |e investigator |4 oth | |
| 700 | 1 | |a Nokes, Tim |e investigator |4 oth | |
| 700 | 1 | |a Rule, Simon |e investigator |4 oth | |
| 700 | 1 | |a Thomas, Wayne |e investigator |4 oth | |
| 700 | 1 | |a Cutting, Robert |e investigator |4 oth | |
| 700 | 1 | |a Joseph, Joe |e investigator |4 oth | |
| 700 | 1 | |a Kaul, Stuti |e investigator |4 oth | |
| 700 | 1 | |a Sorour, Youssef |e investigator |4 oth | |
| 700 | 1 | |a Chvuka, Shingi |e investigator |4 oth | |
| 700 | 1 | |a Mangos, Hilda |e investigator |4 oth | |
| 700 | 1 | |a Neylon, Annette |e investigator |4 oth | |
| 700 | 1 | |a Farrell, Katrina |e investigator |4 oth | |
| 700 | 1 | |a Edwards, Hugh |e investigator |4 oth | |
| 700 | 1 | |a Hanlon, Katharine |e investigator |4 oth | |
| 700 | 1 | |a Fail, Tom |e investigator |4 oth | |
| 700 | 1 | |a Goodrick, Margaret |e investigator |4 oth | |
| 700 | 1 | |a Heartin, Earnest |e investigator |4 oth | |
| 700 | 1 | |a Hoyle, Christine |e investigator |4 oth | |
| 700 | 1 | |a Rye, Adam |e investigator |4 oth | |
| 700 | 1 | |a Carr, Robert |e investigator |4 oth | |
| 700 | 1 | |a Raj, Kavita |e investigator |4 oth | |
| 700 | 1 | |a Krogh Jensen, Morten |e investigator |4 oth | |
| 700 | 1 | |a Janmohamed, Riaz |e investigator |4 oth | |
| 700 | 1 | |a Kaczmarski, Richard |e investigator |4 oth | |
| 700 | 1 | |a Sugai, Taku |e investigator |4 oth | |
| 700 | 1 | |a Ademokun, Debo |e investigator |4 oth | |
| 700 | 1 | |a Chalmers, Isobel |e investigator |4 oth | |
| 700 | 1 | |a Hodson, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Gomez, Cesar |e investigator |4 oth | |
| 700 | 1 | |a Sadullah, Shala |e investigator |4 oth | |
| 700 | 1 | |a Kwan, Mark |e investigator |4 oth | |
| 700 | 1 | |a Longmuir, Karyn |e investigator |4 oth | |
| 700 | 1 | |a Wilson-Morkeh, Isaac |e investigator |4 oth | |
| 700 | 1 | |a Hunter, Ann |e investigator |4 oth | |
| 700 | 1 | |a Martin, Murray |e investigator |4 oth | |
| 700 | 1 | |a Saravanamuttu, Kandeepan |e investigator |4 oth | |
| 700 | 1 | |a Sidra, Gamal |e investigator |4 oth | |
| 700 | 1 | |a Burns, Sarah |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical oncology : official journal of the American Society of Clinical Oncology |d 1986 |g 42(2024), 10 vom: 01. März, Seite 1158-1168 |w (DE-627)NLM012608777 |x 1527-7755 |7 nnns |
| 773 | 1 | 8 | |g volume:42 |g year:2024 |g number:10 |g day:01 |g month:03 |g pages:1158-1168 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1200/JCO.23.00943 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 42 |j 2024 |e 10 |b 01 |c 03 |h 1158-1168 | ||