By: Kerri Fitzgerald
Patients with newly-diagnosed multiple myeloma (MM) treated with isatuximab plus carfilzomib, lenalidomide, dexamethasone (IsaKRD) in induction, consolidation, and light consolidation phases saw sustained measurable residual disease (MRD) negativity, including in those with high-risk disease.
Francesca Gay, MD, PhD, of the University of Torino, presented the findings at the 2025 ASCO(R) Annual Meeting.
Transplant-eligible newly-diagnosed MM patients ages <70 years were included.
The IsaKRd arm (n=151) received:
- Four full-dose IsaKRd induction cycles
- Melphalan plus autologous hematopoietic cell transplant
- Four full-dose IsaKRd consolidation cycles
- Twelve 28-day light consolidation cycles
A control arm (n=151) received KRd in the same schedule used in the experimental arm.
After a median follow-up of 35 months, the intention to treat analysis showed MRD negativity rates at the 10-5 cutoff after full-dose consolidation of 77% with IsaKRd and 67% with KRd (odds ratio [OR], 1.67; P=0.049); MRD rates of 10-5 one year after light consolidation were 66% and 59%, respectively (OR 1.36; P=0.21).
MRD negativity rates at the 10-6 cutoff after full-dose consolidation were 67% with IsaKRd and 48% with KRd (OR, 2.29; P<0.001); MRD rates of 10-6 one year after light consolidation were 52% and 38%, respectively (OR, 1.82; P=0.012).
MRD (10-6) negativity rates were also seen in the high-risk cohort: 62% versus 20% in patients with ≥2 high-risk cytogenic abnormalities (OR, 6.3; 95% CI, 1.11-35.66) and 47% versus 35% in patients with R2-International Staging System III/IV disease (OR, 1.62; 95% CI 0.77-3.41).
During light consolidation, common grade 3/4 hematologic adverse events (AEs) observed in the IsaKRd and KRd arms were neutropenia (17% vs 18%) and thrombocytopenia (2% vs 3%); common 3/4 non-hematologic AEs included infections (8% vs 5%), gastrointestinal impacts (4% vs 4%), and vascular impacts (3% vs 1%).
Among IsaKRd and KRd-treated patients, 3% and 2%, respectively, discontinued treatment due to toxicity; two treatment-related deaths occurred in the IsaKRd arm.
The study is funded by Sanofi and Amgen.
Reference
Gay F, Roeloffzen W, Dimopoulos M, et al. Sustained MRD negativity in patients with newly diagnosed multiple myeloma treated with carfilzomib-lenalidomide-dexamethasone with or without isatuximab (phase III IsKia trial). Abstract #7502. Presented at the 2025 ASCO® Annual Meeting; May 30-June 3, 2025; Chicago.
