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

Design

Randomised phase 3 trial, blinatumomab vs chemotherapy after consolidation; planned interim analysis

Population

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

Primary outcome

Event-free survival (4-year estimate)

Effect

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

In this randomised trial (AIEOP-BFM ALL 2017), 709 of 768 eligible children with newly diagnosed high-risk B-cell acute lymphoblastic leukaemia were randomised after consolidation to two cycles of blinatumomab (358 children) or two cycles of conventional chemotherapy (351). The primary aim was a 10-percentage-point gain in 4-year event-free survival.

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% (63.8 to 75.9) with chemotherapy (P = 0.0002), a hazard ratio of 0.51 (0.35 to 0.73). Treatment-related infection occurred in 23.9% against 69.4% (P < 0.001). Life-threatening adverse events were seen in 0.5% (one fatal) against 4.7%, and neurotoxic events in 12.0% against 3.2%. Grade 2 or higher cytokine release syndrome occurred in 1.1% with blinatumomab.

This is an interim analysis with a median follow-up under three years, so late relapses and long-term toxicity are not captured. The paper does not address the cost or availability of blinatumomab in India, which should be checked with the treating centre.

• Blinatumomab replaced two chemotherapy cycles; it was not simply added on top.
• Estimated 4-year event-free survival was 83.0% vs 70.3% at interim analysis.
• Infections were far less frequent with blinatumomab, and neurotoxicity was more frequent (12.0% vs 3.2%).
• Discuss availability and funding with the treating centre, since the trial does not address them.

Why it matters

It suggests that a targeted immunotherapy can substitute for part of conventional chemotherapy while improving outcomes in this group.

Don't overread it

The result comes from a planned interim analysis with short follow-up; late events are not yet known.

The statistics, in plain English

A hazard ratio of 0.51 means that at any time point, children given blinatumomab had about half the rate of an event (relapse, resistance, second cancer or death). Because this is an interim analysis, the estimate can change as more events accrue.

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