Prediction Of Therapeutic Resistance In Adult Acute Myeloid Leukemia: Analysis Of 4,550 Newly Diagnosed Patients From MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center

• Published in: Blood 2013-11, Vol.122 (21), p.64-64
• Main Authors: Walter, Roland B, Othus, Megan, Burnett, Alan K., Löwenberg, Bob, Kantarjian, Hagop M., Ossenkoppele, Gert J., Hills, Robert K., Ravandi, Farhad, Evans, Anna, Pierce, Sherry R., Appelbaum, Frederick R., Estey, Elihu H.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.64.64

Primary failure of induction chemotherapy or disease recurrence after short remission duration (“therapeutic resistance”) remains the principal problem in adult acute myeloid leukemia (AML). Although cytogenetic and molecular abnormalities have proven useful in the identification of subsets of patients with distinct disease risks, it is unclear to what degree therapeutic resistance can be predicted for individual patients. We used information on patients with newly diagnosed AML other than acute promyelocytic leukemia receiving curative-intent treatment on trials conducted by the U.K. Medical Research Council/National Cancer Research Institute (MRC/NCRI; 1988-2010; n=2,615), the Dutch-Belgian Cooperative Trial Group for Hematology/Oncology and the Swiss Group for Clinical Cancer Research (HOVON/SAKK; 1987-2008; n=1,098), the U.S. cooperative group SWOG (1987-2009; n=428), and MD Anderson Cancer Center (2000-2011; n=409). Achievement of a complete remission (CR) with the initial 1-2 courses of induction chemotherapy was defined as therapeutic success. Patients who failed to achieve CR were defined as primary refractory for the purpose of this analysis; patients who experienced treatment-related mortality (i.e., death within 28 days of treatment initiation) were excluded from this analysis. We used logistic regression analyses to assess the relationship between individual covariates and various measures of therapeutic resistance. The following pre-treatment covariates were used in the regression modeling: age at diagnosis, gender, white blood cell (WBC) count, platelet count, bone marrow blast percentage, disease type (primary vs. secondary), cytogenetic risk, FLT3/NPM1 status, and treatment site. We then used the area under the receiver operator characteristic curve (AUC) to quantify a model's ability to predict therapeutic resistance; in this approach, an AUC of 1 indicates perfect prediction while an AUC of 0.5 indicates no prediction; AUC values of 0.6-0.7, 0.7-0.8, and 0.8-0.9 are commonly considered as poor, fair, and good, respectively. A total of 4,550 patients (median age: 52 years [range: 15-90 years]) were included in this study. A CR to the initial 1-2 courses of induction chemotherapy was achieved in 3,597 (79.1%) of patients, whereas 953 (20.9%) were primary refractory; 1,304/4,497 patients (29.0%) with sufficient follow-up time were either primary refractory or had a relapse-free survival (RFS) of 3 months or less after CR achievement, 1,774/4