Likely new standard of care: Blinatumomab for children with relapsed B-ALL

Children with relapsed B-cell acute lymphoblastic leukaemia (B-ALL) survived significantly longer when treated with immunotherapy agent blinatumomab as post-reinduction consolidation therapy before haematopoietic stem cell transplantation (HSCT) compared with standard chemotherapy.

Prof. Patrick A. Brown (Johns Hopkins Kimmel Cancer Center, Baltimore, USA) presented the results of the randomised, phase 3 AALL1331 trial, which aimed to specifically test the benefits of the bispecific antibody blinatumomab (binding both CD19 expressed on B cells and CD3 expressed on T cells) in children and young adults with minimal residual disease (MRD) after chemotherapy [1]. The unmet need this trial attempted to address was that young patients with MRD are frequently unable to proceed to bone marrow transplant and are consequently prone to relapse and death.

All patients enrolled (n=208; aged 1-30 years) had high- or intermediate-risk B-ALL at first relapse after 1 month of standard chemotherapy. Patients were randomised to either a control arm, which received 2 blocks of intensive chemotherapy (n=103) or 2 cycles of blinatumomab (n=105). Patients were then worked up for HSCT. The primary endpoint of this study was disease-free survival Secondary endpoints were MRD clearance, safety, and bridge to a successful HSCT.

The primary endpoint was met. With a median follow-up of 1.4 years, the disease-free survival of the blinatumomab arm was 59.3% compared with 41.0% with those who received intensive chemotherapy (P=0.050). Overall survival at 2 years was 79.4% and 59.2% with blinatumomab and chemotherapy, respectively (P=0.005).
The secondary endpoints were also met. Blinatumomab significantly improved MRD clearance at both treatment points tested (P<0.0001). No new safety signals were observed for either treatment, although the incidence of serious treatment-related adverse events ≥ grade 3, such as febrile neutropenia, infection, sepsis, or mucositis, was significantly higher in the chemotherapy arm than the blinatumomab arm (P<0.001).

Importantly, given that the best opportunity for a curative treatment is HSCT, the patients in the blinatumomab arm (73%) were more likely to successfully bridge to transplant than those patients in the intensive chemotherapy arm. At the end of the chemotherapy treatment, 45% of participants went on to transplant (P<0.0001).

Prof. Brown: “Based on our study, it appears that blinatumomab is a much more effective bridge to transplant for this patient population, leading to a much larger portion of patients who are actually able to receive a bone marrow transplant. We believe that is the reason for the striking improvement in survival among patients who received blinatumomab.”

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   1. Brown P, et al. A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk (HR/IR) First Relapse of B-Acute Lymphoblastic Leukemia (B-ALL) in Children and Adolescents/Young Adults (AYAs) Demonstrates Superior Efficacy and Tolerability of Blinatumomab: A Report from Children’s Oncology Group Study AALL1331. Abstract LBA-1, 61st ASH Annual Meeting, Orlando, FL, USA, 7-10 December 2019.

Posted on 5 March 202028 March 2024