Patients with newly diagnosed multiple myeloma (NDMM) who are treated with an isatuximab-carfilzomib combination had increased levels of sustained measurable residual disease (MRD) negativity compared with those treated with a combination that didn’t include isatuximab, according to findings presented at the European Hematology Association 2025 Congress.
Researchers with the IsKia trial previously reported that induction and consolidation therapy after autologous hematopoietic cell transplant (AHCT) with a combination of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) led to improved MRD negativity rates.
In the trial, patients who were transplant eligible and younger than 70 years old were randomized to the combination that included isatuximab or the one that did not, said presenting author Francesca Gay, MD, PhD, associate professor of hematology at the University of Torino in Italy.
Across 42 centers, 151 patients were randomized to each group. They received four cycles of Isa-KRd or four cycles of KRd, followed by AHCT, and then four more cycles of their respective combinations. Finally, they received 12 more cycles of their respective combinations but at a lower dose, a phase called light consolidation.
Both groups had a similar rate of discontinuation of the study treatment. Overall, 90% of patients completed the light consolidation phase in the Isa-KRd arm, and 94% in the KRd arm.
Both groups saw some improvement in MRD negativity measured at the 10-5 threshold from the full-dose consolidation phase to the light consolidation phase. For Isa-KRd group, it rose from 77% to 79%, and for the KRd group, it rose from 67% to 74%.
Measured at the 10-6 threshold, the difference between the groups was greater, rising from 68% to 74% after light consolidation for the Isa-KRd group and from 48% to 64% for the KRd group.
The difference was also more noticeable at the 10-6 threshold when it came to MRD negativity at one year — 66% for Isa-KRd versus 59% for KRd at 10-5, and 52% versus 38% at 10-6, Dr. Gay said.
Among those with high-risk disease, 44% in the Isa-KRd and 31% in the KRd group had MRD negativity at 10-6 at one year. Among those with two or more high-risk chromosomal abnormalities, MRD negativity at 10-6 at one year was 62% and 20%, respectively. Dr. Gay cautioned that the high-risk data were based on smaller numbers — about 25 in each group had high-risk disease features, and about 15 in each group had two high-risk abnormalities.
Researchers found no increased risk of toxicity compared with prolonged therapy that didn’t include isatuximab.
“Isa-KRd significantly increased the rate of 10-6, one-year sustained MRD negativity, as compared with KRd, even among high-risk and very high-risk patients,” Dr. Gay said. “The rate of early relapse was low in both arms, supporting the effectiveness of the second-generation proteasome-inhibitor carfilzomib in this setting.”
The findings showed that the more sensitive MRD threshold was more informative when comparing the treatment groups, she added.
“If we use these experimental approaches,” she said, “we may need something that is even more sensitive.”
Dr. Gay reports honoraria and consulting from isatuximab manufacturer Sanofi, as well as AbbVie, Bristol Myers Squibb, Janssen, and other companies.
Reference
Broijl A, Roeloffzen W, Dimopoulos MA, et al. Analysis of sustained MRD negativity in patients with newly diagnosed multiple myeloma treated with carfilzomib-lenalidomide-dexamethasone with or without isatuximab (Phase III IsKia trial). Abstract S208. Presented at the European Hematology Association (EHA) 2025 Congress; June 15, 2025; Milan, Italy.
