In a phase 3 trial, the treatment with blinatumomab of low-risk B-cell acute lymphoblastic leukemia (ALL) among children, adolescents, and young adults did not improve survival compared with standard chemotherapy at first relapse, except among patients with bone marrow relapse. These results were published in the Journal of Clinical Oncology.

The phase 3 AALL1331 trial ( identifier: NCT02101853) randomly assigned 255 pediatric and young adult patients with B-cell ALL to receive chemotherapy with blinatumomab or standard chemotherapy after reinduction. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was overall survival (OS).

The median age at baseline was 11 years, with the majority of patients under the age of 18 and aged 1 to 9 at initial diagnosis. The site of first relapse was most commonly the bone marrow at 68%; of which, 80% of patients had isolated bone marrow relapse and 20% had relapse in the bone marrow and extramedullary. A total of 31.5% of patients had isolated extramedullary relapse.

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At 4 years, the DFS was 61.2% in the blinatumomab arm compared with 49.5% in the standard chemotherapy arm (P =.089). However, among patients with the first relapse occurring within the bone marrow and with or without extramedullary involvement, the DFS was 72.7% with blinatumomab compared with 53.7% with standard chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.30-0.99; P =.015).

The 4-year OS was 90.4% with blinatumomab and 79.6% with standard chemotherapy (P =.11). In the subgroup with bone marrow relapse, regardless of extramedullary involvement, the OS was 97.1% in the blinatumomab group compared with 84.8% with the standard chemotherapy group (P =.020).

In the subgroup with bone marrow relapse, shorter DFS was significantly associated with older age at enrollment (HR, 3.2; 95% CI, 1.4-7.2) and presence of minimal residual disease at the end of reinduction (HR, 2.1; 95% CI, 1.2-3.9). Improved DFS was associated with longer time between diagnosis and relapse (HR, 0.37; 95% CI, 0.19-0.71).

Patients who developed isolated extramedullary relapse, including in the central nervous system or testes, demonstrated similar 4-year DFS and OS between the treatment groups. The 4-year DFS was 36.6% and 38.8% among patients treated with blinatumomab or standard chemotherapy, respectively (P =.62). The OS was 76.5% and 68.8% at 4 years in the blinatumomab and standard chemotherapy groups, respectively (P =.53).

The most common grade 3 or higher adverse events in the blinatumomab group was decreases in white blood cell, neutrophil, and lymphocyte counts. Any grade cytokine release syndrome occurred among a cumulative 15% of patients who received blinatumomab, including 2% that were grade 3 or higher in severity. Encephalopathy and seizure occurred among 29% and 6% of patients, respectively, with 5% and 2% grade 3 or higher in severity.

“AALL1331 establishes that blinatumomab improves DFS and OS for children, adolescents, and young adults with low-risk first B-ALL bone marrow relapse with or without extramedullary disease, defining a new standard of care for these patients,” the authors concluded in their report. However, they acknowledged that new strategies are needed for patients with isolated extramedullary relapse.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.  


Hogan LE, Brown PA, Ji L, et al. Children’s Oncology Group AALL1331: phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol. Published online May 31, 2023. doi: 10.1200/JCO.22.02200