Nigel H Russell, Abin Thomas, Robert K Hills, Ian Thomas, Amanda Gilkes, Nuria Marquez Almuina, Sarah Burns, Lucy Marsh, Paresh Vyas, Marlen Metzner, Nicholas McCarthy, Georgia Andrew, Jennifer Byrne, Rob S Sellar, Richard Kelly, Paul Cahalin, Ulrik Malthe Overgaard, Priyanka Mehta, Mike Dennis, Steven Knapper, Sylvie D Freeman
{"title":"根据老年急性髓细胞性白血病患者的残余疾病状况，使用氟达拉滨、AraC、G-CSF 和依达比星，或克拉利宾加多诺比星和 AraC 加强治疗：NCRI AML18 试验结果。","authors":"Nigel H Russell, Abin Thomas, Robert K Hills, Ian Thomas, Amanda Gilkes, Nuria Marquez Almuina, Sarah Burns, Lucy Marsh, Paresh Vyas, Marlen Metzner, Nicholas McCarthy, Georgia Andrew, Jennifer Byrne, Rob S Sellar, Richard Kelly, Paul Cahalin, Ulrik Malthe Overgaard, Priyanka Mehta, Mike Dennis, Steven Knapper, Sylvie D Freeman","doi":"10.1200/JCO.24.00259","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the survival benefit of chemotherapy intensification in older patients with AML who have not achieved a measurable residual disease (MRD)-negative remission.</p><p><strong>Methods: </strong>Five hundred twenty-three patients with AML (median age, 67 years; range, 51-79) without a flow cytometric MRD-negative remission response after a first course of daunorubicin and AraC (DA; including 165 not in remission) were randomly assigned between up to two further courses of DA or intensified chemotherapy-either fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) or DA with cladribine (DAC).</p><p><strong>Results: </strong>Overall survival (OS) was not improved in the intensification arms (DAC <i>v</i> DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01]; <i>P</i> = .054; FLAG-Ida <i>v</i> DA: HR, 0.86 [95% CI, 0.66 to 1.12]; <i>P</i> = .270); OS at 3 years was 34%, 46%, and 42% for DA, DAC, and FLAG-Ida, respectively. Early deaths and other adverse events were more frequent with FLAG-Ida (9% day 60 deaths <i>v</i> 4% after DA or DAC; <i>P</i> = .032). Of patients entering random assignment, 131 had MRD unknown status. In this subgroup of patients lacking evidence of residual leukemia by flow cytometry, there was no detectable survival advantage from intensification. A planned sensitivity analysis excluding these patients demonstrated a survival benefit for both DAC (HR, 0.66 [95% CI, 0.46 to 0.93]; <i>P</i> = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98]; <i>P</i> = .035); OS at 3 years was 30%, 46%, and 46% for DA, DAC, and FLAG-Ida, respectively. There was a concordant reduction in relapse (DAC <i>v</i> DA: HR, 0.66 [95% CI, 0.45 to 0.98]; <i>P</i> = .039; FLAG-Ida <i>v</i> DA: HR, 0.70 [95% CI, 0.49 to 0.99]; <i>P</i> = .042). DAC benefit was maintained when survival was censored for transplant (<i>P</i> = .042).</p><p><strong>Conclusion: </strong>In this study of older patients with AML considered fit and with evidence of residual disease after first induction, chemotherapy intensification improved survival. DAC intensification was better tolerated than FLAG-Ida.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2400259"},"PeriodicalIF":42.1000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Treatment Intensification With Either Fludarabine, AraC, G-CSF and Idarubicin, or Cladribine Plus Daunorubicin and AraC on the Basis of Residual Disease Status in Older Patients With AML: Results From the NCRI AML18 Trial.\",\"authors\":\"Nigel H Russell, Abin Thomas, Robert K Hills, Ian Thomas, Amanda Gilkes, Nuria Marquez Almuina, Sarah Burns, Lucy Marsh, Paresh Vyas, Marlen Metzner, Nicholas McCarthy, Georgia Andrew, Jennifer Byrne, Rob S Sellar, Richard Kelly, Paul Cahalin, Ulrik Malthe Overgaard, Priyanka Mehta, Mike Dennis, Steven Knapper, Sylvie D Freeman\",\"doi\":\"10.1200/JCO.24.00259\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To evaluate the survival benefit of chemotherapy intensification in older patients with AML who have not achieved a measurable residual disease (MRD)-negative remission.</p><p><strong>Methods: </strong>Five hundred twenty-three patients with AML (median age, 67 years; range, 51-79) without a flow cytometric MRD-negative remission response after a first course of daunorubicin and AraC (DA; including 165 not in remission) were randomly assigned between up to two further courses of DA or intensified chemotherapy-either fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) or DA with cladribine (DAC).</p><p><strong>Results: </strong>Overall survival (OS) was not improved in the intensification arms (DAC <i>v</i> DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01]; <i>P</i> = .054; FLAG-Ida <i>v</i> DA: HR, 0.86 [95% CI, 0.66 to 1.12]; <i>P</i> = .270); OS at 3 years was 34%, 46%, and 42% for DA, DAC, and FLAG-Ida, respectively. Early deaths and other adverse events were more frequent with FLAG-Ida (9% day 60 deaths <i>v</i> 4% after DA or DAC; <i>P</i> = .032). Of patients entering random assignment, 131 had MRD unknown status. In this subgroup of patients lacking evidence of residual leukemia by flow cytometry, there was no detectable survival advantage from intensification. A planned sensitivity analysis excluding these patients demonstrated a survival benefit for both DAC (HR, 0.66 [95% CI, 0.46 to 0.93]; <i>P</i> = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98]; <i>P</i> = .035); OS at 3 years was 30%, 46%, and 46% for DA, DAC, and FLAG-Ida, respectively. There was a concordant reduction in relapse (DAC <i>v</i> DA: HR, 0.66 [95% CI, 0.45 to 0.98]; <i>P</i> = .039; FLAG-Ida <i>v</i> DA: HR, 0.70 [95% CI, 0.49 to 0.99]; <i>P</i> = .042). DAC benefit was maintained when survival was censored for transplant (<i>P</i> = .042).</p><p><strong>Conclusion: </strong>In this study of older patients with AML considered fit and with evidence of residual disease after first induction, chemotherapy intensification improved survival. DAC intensification was better tolerated than FLAG-Ida.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"JCO2400259\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.24.00259\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.24.00259","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Treatment Intensification With Either Fludarabine, AraC, G-CSF and Idarubicin, or Cladribine Plus Daunorubicin and AraC on the Basis of Residual Disease Status in Older Patients With AML: Results From the NCRI AML18 Trial.
Purpose: To evaluate the survival benefit of chemotherapy intensification in older patients with AML who have not achieved a measurable residual disease (MRD)-negative remission.
Methods: Five hundred twenty-three patients with AML (median age, 67 years; range, 51-79) without a flow cytometric MRD-negative remission response after a first course of daunorubicin and AraC (DA; including 165 not in remission) were randomly assigned between up to two further courses of DA or intensified chemotherapy-either fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) or DA with cladribine (DAC).
Results: Overall survival (OS) was not improved in the intensification arms (DAC v DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01]; P = .054; FLAG-Ida v DA: HR, 0.86 [95% CI, 0.66 to 1.12]; P = .270); OS at 3 years was 34%, 46%, and 42% for DA, DAC, and FLAG-Ida, respectively. Early deaths and other adverse events were more frequent with FLAG-Ida (9% day 60 deaths v 4% after DA or DAC; P = .032). Of patients entering random assignment, 131 had MRD unknown status. In this subgroup of patients lacking evidence of residual leukemia by flow cytometry, there was no detectable survival advantage from intensification. A planned sensitivity analysis excluding these patients demonstrated a survival benefit for both DAC (HR, 0.66 [95% CI, 0.46 to 0.93]; P = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98]; P = .035); OS at 3 years was 30%, 46%, and 46% for DA, DAC, and FLAG-Ida, respectively. There was a concordant reduction in relapse (DAC v DA: HR, 0.66 [95% CI, 0.45 to 0.98]; P = .039; FLAG-Ida v DA: HR, 0.70 [95% CI, 0.49 to 0.99]; P = .042). DAC benefit was maintained when survival was censored for transplant (P = .042).
Conclusion: In this study of older patients with AML considered fit and with evidence of residual disease after first induction, chemotherapy intensification improved survival. DAC intensification was better tolerated than FLAG-Ida.
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The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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