Phase II GMMG-CONCEPT trial: Final analysis of Isa-KRd in patients with HR NDMM

Patients with high-risk (HR) newly diagnosed multiple myeloma (NDMM) continue to experience poor survival outcomes despite advances in novel combination therapies. The Multiple Myeloma Hub previously reported preliminary results from the phase II GMMG-CONCEPT trial (NCT03104842). During the European Hematology Association 2025 Congress, Lisa Leypoldt presented the final analysis of the primary endpoint, with a focus on the transplant-eligible cohort, evaluating the efficacy of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in patients with HR NDMM.¹  

A total of 245 patients with HR NDMM were enrolled, including 219 patients in the transplant-eligible cohort, and 26 in the transplant-ineligible cohort. The primary endpoint was measurable residual disease negativity at a sensitivity of 10⁻⁵ after consolidation. A key secondary endpoint was progression-free survival.

Key learnings

The primary endpoint was met, with 74.8% of patients in the TE cohort achieving MRD-negativity after consolidation. Sustained MRD-negativity for ≥1 year and ≥2 years was observed in 67.1% and 44.7% of TE patients, respectively. 

At a median follow-up of 43 months, median PFS in the TE cohort was 72.8 months, while median OS was not reached. Sustained MRD-negativity was associated with prolonged PFS compared with MRD-positivity (hazard ratio, 0.15; p < 0.0001).

Carfilzomib administered weekly at 56 mg/m² resulted in more dose reductions but fewer treatment discontinuations compared with the twice-weekly 36 mg/m² regimen and is recommended in this setting.

Isa-KRd demonstrated deep and durable MRD-negativity, supporting its potential as a standard-of-care regimen for patients with HR NDMM.