Adding isatuximab to carfilzomib and dexamethasone significantly improved progression-free survival (PFS) and the depth of response in patients with relapsed or refractory multiple myeloma, according to a phase 3 trial published in The Lancet.
In the IKEMA trial (ClinicalTrials.gov Identifier: NCT03275285), researchers sought to investigate the benefit of adding isatuximab to carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma treated with 1 to 3 previous lines of therapy.
The study enrolled 302 patients from 69 centers in 16 countries. The patients had a median age of 64 years and had received a median of 2 prior lines of therapy.
The patients were randomly assigned to receive isatuximab plus carfilzomib and dexamethasone (179 patients) or carfilzomib plus dexamethasone (123 patients). The median treatment duration was 80.0 weeks in the isatuximab group and 61.4 weeks in the control group.
At a median follow-up of 20.7 months, the median PFS was not reached in the isatuximab group and was 19.5 months in the control group (hazard ratio, 0.53; 99% CI, 0.32-0.89; P =.0007). The estimated 2-year PFS was 68.9% in the isatuximab group and 45.7% in the control group.
There was no significant difference in overall response rate (ORR) between the groups. The ORR was 87% in the isatuximab group and 83% in the control group (P =.19).
However, the rate of very good partial response or better was significantly higher with isatuximab than without it — 73% and 56%, respectively (P =.0011). The complete response rate was 40% and 28%, respectively.
The rate of minimal residual disease (MRD) negativity in the isatuximab group was more than double the rate of MRD negativity in the control group — 30% and 13%, respectively (P =.0004). The rates of MRD-negative complete response were 20% and 11%, respectively.
Common treatment-emergent adverse events (TEAEs) of any grade (in the isatuximab and control groups, respectively) were hypertension (37% vs 31%), diarrhea (36% vs 29%), and upper respiratory tract infection (36% and 24%). Infusion-related reactions occurred more frequently in the isatuximab group than in the control group (46% vs 3%).
The rate of grade 3 or higher TEAEs was 77% in the isatuximab group and 67% in the control group. The rate of serious TEAEs was 59% and 57%, respectively.
TEAEs led to discontinuation in 8% of the isatuximab group and 14% of the control group. Fatal TEAEs occurred in 3% of patients in both groups.
“Taken together, these results show that isatuximab plus carfilzomib-dexamethasone is a new standard of care for patients with relapsed multiple myeloma,” the authors wrote. “Specifically, the addition of isatuximab to carfilzomib and dexamethasone is a new treatment option for patients with disease progression after an immunomodulatory
drug-containing first-line therapy or those who are refractory to immunomodulatory drugs.”
Disclosures: This research was supported by Sanofi. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomized phase 3 trial. Lancet. Published Online June 4, 2021. doi: 10.1016/S0140-6736(21)00592-4