PASS ALL study: Pediatric-inspired vs adult regimens in AYA patients with high-risk Ph− B-ALL

Although considerable progress has been made in the treatment and outcomes of childhood acute lymphoblastic leukemia (ALL), outcomes for adult patients with ALL remain poor. This may be attributed to the differences in chemotherapy protocols. Pediatric-inspired protocols have improved outcomes for adolescents and young adults; however, the effect of this regimen in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unknown.¹

Here, we summarize an observational, multicenter cohort PASS ALL study published by Wang et al.¹ in British Journal of Haematology investigating the effect of pediatric-inspired vs adult chemotherapy regimens on survival outcomes in adult patients with high-risk Philadelphia chromosome-negative (Ph−) B-cell ALL (B-ALL).

Study design¹

• This study included patients aged 14–60 years with high-risk Ph− B-ALL and were eligible for allo-HSCT.
• Treatment included either PDT-ALL-2016 (pediatric-inspired) or CALLG-2008 protocol (adult regimen).
• The primary endpoint was leukemia-free survival (LFS).
• Secondary endpoints included overall survival, non-relapse mortality, and side effects.

Key findings¹

• A total of 143 patients were included in the study, 77 of which received a pediatric-inspired regimen and 66 received an adult regimen.
• Overall, 128 patients underwent allo-HSCT.

• Early deaths were reported in 2% and 4.5% of patients in the pediatric-inspired and adult regimen cohort, respectively.
• The complete remission rate was 92.4% vs 86.4% in the pediatric-inspired and adult regimen cohort, respectively.
• Negative measurable residual disease status by flow cytometry was achieved by 79.7% of patients in the pediatric-inspired cohort vs 77.9% in the adult regimen cohort.
• There was a significant difference in the LFS and cumulative incidence of relapse between the two cohorts
  • 3-year LFS (p = 0.001), overall survival (p = 0.074), cumulative incidence of relapse (p = 0.000), and non-relapse mortality (p = 0.347) rates are reported in Figure 1.

Multivariate analyses showed that pediatric-inspired regimen is a predictive factor for LFS with a hazard ratio of 3.073 (95% Cl [confidence interval], 1.600–5.902; p = 0.001) as well as first complete remission disease status with a hazard ratio of 1.543 (95% Cl, 1.192–1.996; p = 0.001).

CIR, cumulative incidence of relapse; LFS, leukemia-free survival; OS, overall survival; NRM, non-relapse mortality.
*Adapted from Wang, et al.¹

Key learnings
Pediatric-inspired chemotherapy regimens achieved durable responses and improved outcomes in adult patients with high-risk Ph− B-ALL undergoing allo-HSCT compared with conventional adult protocols.