Blood 2019-04-04
A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403.
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.
Related Questions
Do you use G-CSF for a patient with ALL admitted for febrile neutropenia with prolonged count recovery?
I agree with this response. To highlight one other consideration: G-CSF is not routinely given during COG-based, pediatric-inspired therapy like the C10403 regimen (Stock et al., PMID 30658992). However, when patients treated with this approach in our system develop neutropenic fever, we will usuall...
In patients with Philadelphia-negative ALL who are transplant ineligible, is there any data to guide the duration of maintenance POMP therapy?
To my knowledge, there have not been any prospective trials in the modern era that specifically address the issue of the duration of maintenance therapy in adults with ALL.Most regimens that have been studied provide a timeframe over which maintenance therapy should be administered, and nearly all h...
When during ALL induction therapy are you checking for MRD?
It is generally advisable to measure MRD from a bone marrow aspirate at the end of the first course of therapy for ALL. If a pediatric-inspired regimen such as CALGB 10403 is being used, undetectable MRD after Remission Induction (i.e., approximately Day 28) is associated with an excellent rate of d...
Do you prefer hyper-CVAD or the CALGB 9111 protocol for high intensity remission induction treatment in Ph-negative ALL patients?
It depends on the patient's age. Historically, the adolescents and young adults (AYAs) population, arbitrarily defined by the National Cancer Institute as those between the ages of 15 to 39 years old, had worse outcomes compared to children with B-ALL (EFS of 30-40%). This is largely driven by adver...