Background
CALGB 10403 was a phase II single-arm trial testing a pediatric-inspired COG (AALL0232 backbone) regimen in adolescents and young adults (AYA) aged 17–39 with newly diagnosed Ph-negative B- or T-cell ALL. Retrospective data had consistently shown AYA patients treated on pediatric-style regimens (intensified asparaginase, vincristine, corticosteroids) had far better outcomes than those on adult regimens. CALGB 10403 was the first prospective US cooperative-group trial to formally test a pediatric ALL regimen exclusively in the AYA population.
Interventions and follow up
Regimen: Pediatric-inspired COG regimen — multi-agent intensive chemotherapy with vincristine, PEG-asparaginase, corticosteroids, anthracyclines, methotrexate, mercaptopurine, plus CNS prophylaxis (IT methotrexate/cytarabine), over ~2.5–3 years (n=295)
Population: AYA aged 17–39, newly diagnosed Ph-negative ALL
Primary endpoint: Event-free survival; secondary: OS, toxicity, CNS relapse
mFollow up: ~5 years
Population: AYA aged 17–39, newly diagnosed Ph-negative ALL
Primary endpoint: Event-free survival; secondary: OS, toxicity, CNS relapse
mFollow up: ~5 years
Results
2-yr EFS: 66% (median EFS 78.1 months)
3-yr EFS: 59%, 95% CI 53–65%
3-yr OS: 73%, 95% CI 68–79%
Historical adult CALGB comparison: EFS roughly doubled (historical ~34%)
CNS relapse: <5%
3-yr EFS: 59%, 95% CI 53–65%
3-yr OS: 73%, 95% CI 68–79%
Historical adult CALGB comparison: EFS roughly doubled (historical ~34%)
CNS relapse: <5%
Adverse events
Asparaginase-related: hepatotoxicity ~35%, venous thromboembolism ~12%, osteonecrosis ~6%
Metabolic/infectious: corticosteroid hyperglycemia ~20%; Grade ≥3 infections during induction ~20%
Mortality: treatment-related mortality low (~2–3%), not increased vs historical adult regimens
Metabolic/infectious: corticosteroid hyperglycemia ~20%; Grade ≥3 infections during induction ~20%
Mortality: treatment-related mortality low (~2–3%), not increased vs historical adult regimens
Conclusions
A pediatric-inspired ALL regimen achieved a 3-year EFS of 59% and OS of 73% in AYA patients aged 17–39 with newly diagnosed Ph-negative ALL, substantially exceeding historical adult-regimen outcomes and providing prospective validation that AYA ALL patients benefit from pediatric-style treatment intensity across the full 17–39 age range.
Key Limitations
Single-arm phase II with no concurrent randomized comparator; historical comparison biased by era effects (improved supportive care, MRD-stratified therapy); excludes Ph+ ALL and Burkitt; long complex regimen with substantial toxicity (hepatotoxicity, VTE, osteonecrosis, hyperglycemia) requiring asparaginase expertise; EFS/OS remain inferior to childhood ALL (5-yr EFS ~90%); contemporary regimens now add blinatumomab/inotuzumab (E1910); CAR-T active at relapse; Ph-like ALL (CRLF2/JAK) not stratified or targeted.
Clinical Context
CALGB 10403 established a de facto standard of care for AYA Ph-negative ALL (age 17–39) in the US, prompting many adult oncology programs to adopt pediatric-inspired regimens for this group. The subsequent ECOG-ACRIN E1910 trial (2022) added blinatumomab consolidation to chemotherapy in MRD-negative Ph-negative B-ALL and improved OS, representing the next evolution. Ph+ ALL is now managed with TKI-containing chemo-light or chemo-free regimens (dasatinib + blinatumomab, GIMEMA LAL2116). CALGB 10403 remains the foundational prospective evidence for the pediatric-inspired approach in AYA ALL.
References