IKEMA is a randomized, open-label, multicenter, phase 3 study that investigated isatuximab plus carfilzomib and dexamethasone (Isa-Kd) in patients with relapsed/refractory multiple myeloma (RRMM) who received 1 to 3 prior lines of therapy. Based on the primary interim analysis of IKEMA, Isa-Kd is approved for the treatment of patients with RRMM who have received ≥1 prior lines of therapy. At the 2022 International Myeloma Society meeting, updated, longer-term depth of response results were presented, which included minimal residual disease (MRD) negativity status, commonly associated with improved progression-free survival (PFS) and overall survival.
In IKEMA, 179 patients with RRMM were randomly assigned to Isa-Kd, and 123 patients were assigned to Kd alone. The primary end point in this prespecified analysis was PFS at 159 events. Secondary end points included ≥complete response ([CR] + stringent CR), MRD negativity (10-5), and CR plus MRD negativity.
After a median follow-up of 44 months, a PFS benefit was observed with Isa-Kd versus Kd: 35.7 months versus 19.2 months (hazard ratio, 0.58; 95% confidence interval [CI], 0.42-0.79). ≥CR was 44.1% in the Isa-Kd group versus 28.5% in the Kd alone group (odds ratio [OR], 2.09; 95% CI, 1.26-3.48; descriptive P = .0021). In addition, MRD negativity occurred in 33.5% of the Isa-Kd group and only 15.4% of the Kd alone group (OR, 2.78; 95% CI, 1.55-4.99; descriptive P = .0002). In the Isa-Kd group, MRD negativity rates were higher in certain patients, including those with advanced age, renal impairment, higher International Staging System stage at diagnosis, 1q21+ chromosome, more lines of prior therapy, and refractoriness to lenalidomide. A total of 26.3% of patients in the Isa-Kd group reached ≥CR plus MRD negativity compared with 12.2% in the Kd alone group (OR, 2.57; 95% CI, 1.35-4.88; P = .0015). A longer median PFS was seen in both arms among MRD-negative patients versus MRD-positive patients.
Deeper responses were observed with Isa-Kd compared with Kd alone. A ≥CR rate of 44.1% and a ≥CR plus MRD negativity rate of 26.3% in the Isa-Kd group are the highest reported responses to date for a proteasome inhibitor ̶ based regimen in this patient population. In both arms, MRD negativity was associated with better outcomes and a longer median PFS. These findings clearly support Isa-Kd as standard of care in patients with RRMM with ≥1 prior lines of treatment.
Source:
Hajek R, Moreau P, Auguston B, et al. Depth of response of isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma: IKEMA updated analysis. Oral abstract presented at: International Myeloma Foundation; August 25-27, 2022; Los Angeles, CA.