Journal: Nature medicine
Phase 3 EMN24 IsKia trial: transplant-eligible newly diagnosed multiple myeloma (≤70 years)
Design
- Randomization: 302 patients randomized 1:1
- Arms:
- Isa-KRd: isatuximab + carfilzomib + lenalidomide + dexamethasone
- KRd: carfilzomib + lenalidomide + dexamethasone
- Treatment phases: induction before ASCT and consolidation after ASCT
- Primary endpoint: NGS-based MRD negativity (10⁻⁵ sensitivity) after consolidation
- Key secondary endpoints: MRD negativity after induction and progression-free survival (PFS); deeper MRD thresholds (10⁻⁶) were exploratory
Efficacy
- Post-consolidation MRD negativity:
- At 10⁻⁵: 77% with Isa-KRd vs 67% with KRd (OR 1.67, P=0.049)
- At 10⁻⁶: 68% vs 48% (OR 2.36, P=0.0004)
- Post-induction MRD negativity (rapid depth of response):
- At 10⁻⁵: 46% vs 27% (OR 2.32, P=0.0007)
- At 10⁻⁶: 28% vs 14% (OR 2.44, P=0.0029)
- One-year sustained MRD negativity (10⁻⁵): 52% vs 38% (OR 1.82, P=0.012)
- PFS: data are not yet mature
Safety
- Grade 3–4 non-hematologic adverse events, treatment discontinuations, and AE-related deaths were similar between arms.
Clinical takeaway
- Adding isatuximab to KRd for induction and post-transplant consolidation in transplant-eligible NDMM significantly increases the depth and durability of MRD negativity, including at 10⁻⁶ sensitivity, with a safety profile comparable to KRd alone. PFS benefit is not yet established pending longer follow-up.