Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD <10−3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.