The phase III IsKia trial evaluated Isatuximab-carfilzomib-lenalidomide-dexamethasone (IsaKRd) vs KRd for transplant-eligible NDMM patients. IsaKRd significantly increased MRD negativity rates post-induction and consolidation. Light consolidation maintained 10-6 sustMRD negativity advantage, particularly in high-risk cytogenetic subgroups. Safety profiles were manageable with expected hematologic and non-hematologic adverse events.

Key Points:

• Research Problem/Question: Evaluate IsaKRd vs KRd efficacy in achieving MRD negativity.
• Methodology: Phase III trial with IsaKRd induction, consolidation, and light consolidation phases.
• Key Findings: Higher rates of 10-6 sustMRD negativity with IsaKRd vs KRd, manageable safety profile.
• Significance/Impact: Significant improvement in MRD outcomes, especially in high-risk NDMM patients.

Conclusion:
IsaKRd demonstrated superior MRD negativity rates compared to KRd, offering a promising treatment option for transplant-eligible NDMM patients, including those with high-risk cytogenetics.

Authors:
Francesca Gay, Wilfried Roeloffzen, Meletios Dimopoulos, Laura Rosiñol, Marjolein van der Klift, Albert Oriol, Eirini Katodritou, Ka-Lung Wu, Paula Rodríguez-Otero, Roman Hajek, Elena M. van Leeuwen-Segarceanu, Elena Zamagni, Niels van de Donk, Katja Weisel, Fredrik Schjesvold, Joan Blade, Hermann Einsele, Pieter Sonneveld, Mario Boccadoro, Annemiek Broijl.

Clinical Trial Registration Number: NCT04483739
DOI: 10.1200/JCO.2025.43.16_suppl.7502
Abstract #7502