Presentation (CTI)

OBJECTIVES: Minimal residual disease (MRD) is gaining recognition as a regulatory endpoint in hemato-oncology; it was accepted by the FDA as an endpoint for accelerated approval in multiple myeloma (MM). HTA agencies prefer established endpoints such as PFS; we asked how often will HTA agencies be faced with MRD as a primary endpoint in future assessments.
METHODS: Clinicaltrials.gov was searched for interventional trials including MRD as an endpoint. For trials with MRD as a primary endpoint, European marketing authorization status was reviewed and HTA websites searched for corresponding assessments.
RESULTS: Hemato-oncology trials including MRD as an endpoint have grown from 10 initiating in 2010 to 75 in 2024. Relatively few trials include MRD as a primary endpoint, this was most common in MM trials (3-25% of MM trials/year in recent years), followed by AML and CLL. As of June 2025 only a single trial with MRD as a primary endpoint had been through HTA (NCT03109093).In April 2025 the European Commission approved a quadruplet regimen including daratumumab for newly-diagnosed MM based on the CEPHEUS trial, with MRD negativity as a primary endpoint. CHMP noted that despite MRD negativity not being robustly confirmed as a surrogate endpoint for PFS in NDMM, PFS results supported MRD negativity rate.
CONCLUSIONS: MRD is an important endpoint for accelerating access to innovative therapies. The increasing inclusion of MRD as a primary endpoint potentially reflects the expectation of its acceptance by regulators and clinicians, and value to patients . However, while several HTA agencies have commented on MRD in prior evaluations, it remains to be seen how HTA agencies will react and what level of maturity of PFS or other evidence is required to support positive recommendations. Ongoing and future HTA deliberations will be critical in accelerating patient access by reducing time to obtain final endpoint data.