Presented by Lisa Leypoldt and awarded one of the Best Young EHA Abstract Awards, the Phase II CONCEPT trial has delivered encouraging results for patients with high-risk newly diagnosed multiple myeloma (NDMM). This prospective, multicentre trial evaluated the intensified first-line treatment regimen Isa-KRd (isatuximab, carfilzomib, lenalidomide, dexamethasone) in patients with poor prognosis due to high-risk cytogenetic abnormalities.
The study enrolled 219 transplant-eligible (TE) and 26 transplant-ineligible (TNE) adult patients, all presenting with at least one high-risk cytogenetic aberration combined with advanced disease stage. Patients underwent induction with Isa-KRd, followed by intensification through either high-dose melphalan and autologous stem cell transplant (TE group) or further Isa-KRd cycles (TNE group). Consolidation and maintenance phases continued with Isa-KRd.
At data cut-off, the trial met its primary endpoint with a minimal residual disease (MRD) negativity rate of 73.2% post-consolidation in the TE population, a significant improvement over the predefined 50% threshold. Sustained MRD negativity for over one and two years was observed in 64.8% and 40.6% of patients respectively. Median progression-free survival for TE patients reached 69.7 months, while median overall survival has not yet been reached.
Notably, the trial found that a once-weekly dosing schedule of carfilzomib was better tolerated, reducing treatment discontinuations. This large, purely high-risk NDMM cohort highlights Isa-KRd as a promising standard of care in a patient group historically lacking effective first-line options.
The CONCEPT trial is sponsored by University Medical Center Hamburg Eppendorf with funding and drug supply by Sanofi, Amgen and BMS/Celgene.
Helena Bradbury, EMJ
Reference
Leypoldt L et al. Abstract S209. EHA 12-15 June 2025, Milan, Italy.
