A report from Children’s Oncology Group (COG) AALL1731 study showed that paediatric patients with standard-risk (SR) B-cell acute lymphoblastic leukaemia (B-ALL) with undetectable minimal residual disease (MRD) at end of induction (EOI) by flow cytometry (FC) but not high-throughput sequencing (HTS) had inferior outcomes on chemotherapy alone, which were partially but not entirely mitigated by blinatumomab. In addition, outcomes of chemotherapy-only treatment among patients with MRD by HTS were not superior to those of patients with detectable MRD.
MRD is one of the most powerful prognosticators in childhood B-ALL. [Blood 2010;115:3206-3214] It has traditionally been measured by FC or polymerase chain reaction–based methods, but detection by HTS has higher analytic sensitivity and lower false-negative rate and is becoming more widely used. [Blood 2017;131:1350-1359]
“In the present ALL1731 analysis, we aimed to prospectively determine the prognostic significance of EOI undetectable HTS MRD, as well as the prognostic significance of FC vs HTS MRD discordance [ie, MRD <0.01 percent by FC but ≥0.01 percent by HTS],” stated first author, Dr Sumit Gupta, Division of Haematology-Oncology, University of Toronto, Toronto, Canada. “We also wanted to determine the impact of blinatumomab on the prognostic value of each of the above.”
AALL1731 enrolled de novo National Cancer Institute SR B-ALL patients aged 1–9.9 years with initial white blood cell count <50,000/μL, without BCR::ABL1, central nervous system (CNS) leukaemia, or testicular disease. After three-drug induction, patients were assigned to risk groups based on somatic genetics, CNS status, day 8 blood FC MRD, and EOI bone marrow (BM) FC MRD. Patients at average relapse risk (SR-AVG) with EOI BM FC MRD <0.01 percent and undetectable HTS MRD (n=162) were nonrandomly assigned to standard-intensity chemotherapy. The remaining 705 SR-AVG patients were randomized to receive standard chemotherapy with (n=353) or without (n=352) two cycles of blinatumomab. [Gupta S, EHA 2026, abstract S112]
After a median follow-up of 3.9 years, the 4-year disease-free survival rates with chemotherapy alone were 94.9 vs 90.4 percent among patients with undetectable HTS MRD (n=160) vs SR-AVG patients with detectable HTS MRD (n=352). “While those rates are numerically different, … there was not a statistically significant difference [p=0.37] between these groups at this point,” reported Gupta.
Patients with detectable HTS MRD treated with chemotherapy plus blinatumomab had a 4-year DFS rate of 95.5 percent, which was statistically significantly better than the 90.4 percent rate of patients who received chemotherapy only (p=0.049).
“Unsurprisingly, outcomes of patients with concordant MRD results by FC and HTS [n=626] were superior to those who had discordant MRD [n=79],” shared Gupta. “The respective 4-year DFS rates were 93.9 vs 85.4 percent [p=0.005].” Among patients randomized to chemotherapy, the rates were 80.0 percent for those with discordant results (n=33) and 91.5 percent for those with concordant results (n=319) (p=0.02). In those who also received blinatumomab, the rates were 89.4 vs 96.4 percent (p=0.05).
Referring to previously published research, Gupta said: “There really doesn't seem to be a subgroup of patients that doesn't derive some benefit from blinatumomab. So, unless you know that a group has outstanding outcomes, with 4-year DFS of ≥95 percent with chemotherapy alone, it is plausible to think that those patients will benefit from blinatumomab. The decision to give blinatumomab comes down to whether you think that 94 percent is not optimal enough for patients with undetectable HTS MRD.” [N Engl J Med 2025;392:875-891; N Engl J Med 2024;391:320-333]