A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403
Wendy Stock, Selina M Luger, Anjali S Advani, Jun Yin, Richard C Harvey, Charles G Mullighan, Cheryl L Willman, Noreen Fulton, Kristina M Laumann, Greg Malnassy, Elisabeth Paietta, Edy Parker, Susan Geyer, Krzysztof Mrózek, Clara D Bloomfield, Ben Sanford, Guido Marcucci, Michaela Liedtke, David F Claxton, Matthew C Foster, Jeffrey A Bogart, John C Grecula, Frederick R Appelbaum, Harry Erba, Mark R Litzow, Martin S Tallman, Richard M Stone, Richard A Larson, Wendy Stock, Selina M Luger, Anjali S Advani, Jun Yin, Richard C Harvey, Charles G Mullighan, Cheryl L Willman, Noreen Fulton, Kristina M Laumann, Greg Malnassy, Elisabeth Paietta, Edy Parker, Susan Geyer, Krzysztof Mrózek, Clara D Bloomfield, Ben Sanford, Guido Marcucci, Michaela Liedtke, David F Claxton, Matthew C Foster, Jeffrey A Bogart, John C Grecula, Frederick R Appelbaum, Harry Erba, Mark R Litzow, Martin S Tallman, Richard M Stone, Richard A Larson
Abstract
Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children's Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response. Median age was 24 years (range, 17-39 years). Use of the pediatric regimen was safe; overall treatment-related mortality was 3%, and there were only 2 postremission deaths. Median event-free survival (EFS) was 78.1 months (95% confidence interval [CI], 41.8 to not reached), more than double the historical control of 30 months (95% CI, 22-38 months); 3-year EFS was 59% (95% CI, 54%-65%). Median overall survival (OS) was not reached. Estimated 3-year OS was 73% (95% CI, 68%-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and presence of the Philadelphia-like gene expression signature. Use of a pediatric regimen for AYAs with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00558519.
Conflict of interest statement
Conflict-of-interest disclosure: W.S. served on advisory boards for Pfizer, Amgen, and Jazz Pharmaceuticals; S.M.L. received clinical trial support from Onconova, Celgene, Cyclacel, Hoffman-La Roche, Onconova, Incyte, Biosight, and Kura and served on an advisory board for Pfizer; A.S.A. received honoraria from Pfizer, Sigma Tau, and Jazz Pharmaceuticals; C.G.M. received honoraria from Amgen and Pfizer; E. Parker owns stock in Teva Pharmaceuticals and Johnson & Johnson; M.S.T. received research funding from AbbVie, AROG, Cellerant, Orsenix, ADC Therapeutics, and Biosight and served on advisory boards for Daiicho-Sankyo, Orsenix, KAHR, Rigel, Abbvie, and Nohla. The remaining authors declare no competing financial interests.
© 2019 by The American Society of Hematology.
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Source: PubMed