Blinatumomab in place of two chemotherapy cycles improved event-free survival in high-risk childhood ALL

Design

Randomised, open-label phase 3 trial (AIEOP-BFM ALL 2017); planned interim analysis at median 2.9 years

Population

709 children with newly diagnosed high-risk B-cell ALL (358 blinatumomab, 351 chemotherapy)

Primary outcome

Event-free survival at 4 years

Effect

83.0% vs 70.3%; HR 0.51 (95% CI 0.35 to 0.73)

In this randomised trial, children with newly diagnosed high-risk B-cell acute lymphoblastic leukaemia received, after consolidation, either two cycles of blinatumomab (a CD19-directed bispecific T-cell engager) or two further cycles of conventional chemotherapy. Of 768 eligible patients, 709 were randomised: 358 to blinatumomab and 351 to chemotherapy.

At a planned interim analysis with a median follow-up of 2.9 years, estimated 4-year event-free survival was 83.0% (95% CI 77.4 to 87.4) with blinatumomab and 70.3% (95% CI 63.8 to 75.9) with chemotherapy, a hazard ratio of 0.51 (95% CI 0.35 to 0.73). The safety pattern differed. Treatment-related infection was far lower with blinatumomab (23.9% vs 69.4%), and life-threatening adverse events occurred in 0.5% vs 4.7%. Neurotoxic events were higher (12.0% vs 3.2%), and grade 2 or higher cytokine release syndrome occurred in 1.1%.

The benefit is measured at an interim analysis, and overall survival and longer-term toxicity are not reported in the abstract. For clinicians outside paediatric oncology, the relevance is that treatment protocols for childhood leukaemia are shifting towards less chemotherapy exposure, with different toxicities to recognise. Access and cost in India are not addressed.

• Refer children with suspected or confirmed leukaemia early to a paediatric oncology centre; protocols are changing quickly.
• Expect fewer chemotherapy-related infections but more neurological adverse events on blinatumomab-based protocols.
• Ask survivors' families about neurological symptoms during and after treatment.
• Do not change an ongoing protocol on this report; the decision sits with the treating team.

Why it matters

It shows that replacing cycles of toxic chemotherapy can improve survival and not only reduce side effects.

Don't overread it

This is a planned interim analysis; long-term survival, late effects and cost-effectiveness are not yet known.

The statistics, in plain English

A hazard ratio of 0.51 means that, at any point, about half as many children had relapse, a second cancer or death compared with the chemotherapy group. The 4-year percentages (83.0% vs 70.3%) are model estimates from an interim analysis with median follow-up of under 3 years, so they will be updated as follow-up grows.

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