Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses

To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemothe...

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Veröffentlicht in:Journal of clinical oncology 2022-03, Vol.40 (8), p.847-854
Hauptverfasser: Norsworthy, Kelly J, Gao, Xin, Ko, Chia-Wen, Pulte, E Dianne, Zhou, Jiaxi, Gong, Yutao, Shen, Yuan Li, Vallejo, Jonathon, Gwise, Thomas E, Sridhara, Rajeshwari, Deisseroth, Albert B, Farrell, Ann T, de Claro, R Angelo, Blumenthal, Gideon M, Pazdur, Richard
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Sprache:eng
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Zusammenfassung:To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy. We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies. In trial-level analyses, association between HR for OS and OR for CR was moderate (R = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37). On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect.
ISSN:0732-183X
1527-7755
DOI:10.1200/JCO.21.01548