Simplifying the Backbone to Accelerate AML Innovation: Insights from the French BIG-1 Study

Actualités - 19/12/2025

What If AML Innovation Started with a Simpler Backbone?

At ASH25, new results from the French BIG-1 intergroup challenge a deeply rooted assumption in acute myeloid leukemia (AML) development: that innovation must begin with new molecules.

Instead, BIG-1 proposes something more structural, a simplified, robust therapeutic backbone designed to create the conditions for faster, more reliable innovation.

Led by the French intergroup FILO, ALFA, and SFGM-TC, this work redefines induction not as a moving target, but as a stable platform on which future therapies can be meaningfully evaluated.

A Streamlined Induction Platform, Prospectively Validated

The BIG-1 strategy is deliberately simple:

? A single-cycle anthracycline-based induction, followed by IDAC consolidation,
validated in more than 2,000 prospectively enrolled younger AML patients.

This is not simplification by approximation. It is simplification by design—built to be:

  • reproducible across centers,

  • robust across biological subtypes,

  • and sufficiently standardized to serve as a reference backbone.

In a field where heterogeneity often blurs signal detection, this matters.

Why the Backbone Matters More Than It Seems

In early-phase and add-on trials, variability in induction regimens is not neutral. It introduces noise, complicates interpretation, and weakens comparative claims.

By stabilizing the backbone, BIG-1 delivers precisely what next-generation development requires:
? a consistent baseline against which the true added value of new agents can be measured.

This reframes innovation not as stacking complexity, but as controlling it.

What This Means for Industry and Translational Research

Through the Institut Carnot OPALE consortium, partners gain access to a large, deeply annotated national AML cohort, embedded within the BIG-1 framework.

This infrastructure includes:

  • comprehensive genomic profiling,

  • longitudinal MRD monitoring,

  • detailed transplant data.

Such integration creates an environment particularly well suited for:

  • add-on therapeutic strategies,

  • early-phase combination trials,

  • biomarker-driven and response-adaptive development.

Crucially, these elements are not retrofitted, they are structurally embedded.

Creating Space for Meaningful Innovation

BIG-1 does not compete with innovation.
It creates space for it.

By simplifying and stabilizing the therapeutic backbone, the study reduces methodological friction and allows new agents to be evaluated on what truly matters: their incremental clinical and biological contribution.

In that sense, BIG-1 is less a trial than a platform one designed to support the next generation of AML therapeutics with rigor and clarity.

 

? ASH Abstract #0043