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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, Kryzsztof 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 and Richard A. Larson

Key points

  • Feasibility of using an intensive pediatric regimen for AYAs with ALL.

  • High rates of EFS and OS compared to historical controls.

Abstract

Retrospective studies have suggested that older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) had better survival rates when treatment was administered 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 Children's Oncology Group study AALL0232. From 2007-2012, 318 patients enrolled; 295 were eligible and evaluable for response. The median age was 24 years (range, 17-39). Use of the pediatric regimen was safe; overall treatment-related mortality was 3% and there were only two post-remission deaths. The median event-free survival (EFS) is 78.1 months (95% CI, 41.8-not reached), which is more than double the historical control of 30 months (95% CI, 22-38). The 3-year EFS is 59% (95% CI, 54-65%) The median overall survival (OS) has not been reached. The estimated 3-year overall survival is 73% (95% CI, 68-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and the presence of the Philadelphia-like gene expression signature. The use of a pediatric regimen for young adults with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared to historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYA ALL. ClinicalTrials.gov Identifier: NCT00558519

  • Submitted October 23, 2018.
  • Accepted January 4, 2019.