Blinatumomab superior to chemotherapy as consolidation therapy in children with relapsed B-ALL

March 2021 Clinical trials Tobias Rawson

Consolidation therapy for relapsed B-cell acute lymphoblastic lymphoma (ALL) can involve multiple cycles of chemotherapy agents, which represents a significant toxicity burden for these patients. Meanwhile, the bispecific T-cell engager blinatumomab has already shown efficacy in paediatric patients with relapsed or refractory B-cell ALL, although the efficacy of this immunotherapy in a maintenance regimen is uncertain. Recently published through the JAMA Network, a phase III study now ratifies the efficacy of blinatumomab in a maintenance regimen setting, with superior survival outcomes compared to standard chemotherapy.

108 patients with high-risk, first-relapse B-cell ALL who were previously in morphologic complete remission or with M2 marrow (≥5%-<25% blasts), who were also receiving consolidation therapy were enrolled and randomised 1:1 to receive blinatumomab (15 μg/m2/d for 4 weeks, continuous intravenous infusion) or standard chemotherapy, as their third cycle of consolidation therapy, before allogeneic haematopoietic stem cell transplant. The primary endpoint of this study was event-free survival (events: relapse, death, second malignancy or failure to achieve complete remission), with a key secondary endpoint on overall survival. Other secondary endpoints included minimal residual disease remission and safety.

26% reduction in incidence of events with blinatumomab

At a median follow-up of 22.4 months, the incidence of events was 31% vs. 57% in those who received blinatumomab and chemotherapy, respectively (HR[95%CI]: 0.33[0.18-0.61], P< 0.001). Overall survival was also improved with blinatumomab compared to chemotherapy (HR[95%CI]: 0.43[0.18-1.01]), with 14.8% of blinatumomab patients having died at the time of this analysis, compared to 29.6% of those who received chemotherapy. Furthermore, a minimal residual disease remission was achieved at a greater rate in those who received blinatumomab (90% vs. 54%, respectively). Blinatumomab was also safer, compared to chemotherapy, with an incidence of grade ≥ 3 adverse events of 57.4% and 82.4%, respectively. Similarly, the incidence of serious adverse events were 24.1%and 43.1%. However, adverse events leading to treatment discontinuation did occur in 2 patients receiving blinatumomab and no fatal adverse events were reported in either group.

Conclusion

In paediatric patients with B-cell ALL, consolidation therapy with blinatumomab offered better survival outcomes, compared to a multidrug chemotherapy regimen. Importantly, these efficacious results came with a superior safety profile, indicating a less severe treatment burden for these patients. 

Reference:

Locatelli F et al., Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia. JAMA Network. 2021; 325(9): 843-854.

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