Adding isatuximab to carfilzomib and dexamethasone improved progression-free survival (PFS) over the doublet in patients with multiple myeloma, regardless of early or late relapse, according to a subgroup analysis of the phase III IKEMA study.
Lead author Thierry Facon, MD, of the Lille University Hospital in France, and senior author Thomas Martin, MD, of the University of California, San Francisco, presented the subgroup analysis results during the 2022 American Society of Hematology Annual Meeting and Exposition.
The final PFS analysis of the IKEMA study confirmed adding isatuximab to carfilzomib and dexamethasone significantly improved PFS over carfilzomib and dexamethasone in patients with relapsed multiple myeloma. The investigators conducted the IKEMA subgroup analysis to examine updated efficacy and safety of the doublet and triplet in patients with multiple myeloma who had an early relapse or a late relapse.
The study’s investigators randomized patients 3:2 to receive the triplet (n=179) or the doublet (n=123), with treatment continuing until disease progression or unacceptable toxicity. All patients in the subgroup analysis received one to three previous lines of therapy.
The researchers defined early relapse as a relapse that occurred less than a year from the start of the most recent line of therapy for patients with at least two prior lines of therapy, a relapse that occurred less than 18 months for patients with one prior line of therapy, or a relapse that occurred less than a year after autologous hematopoietic stem cell transplantation. They defined a late relapse as occurring a year or more after initiation of the most recent line of therapy for patients with at least two prior lines of therapy, or as a relapse that occurred at least 18 months in patients with one prior line of therapy.
The study included 107 patients with early relapse and 176 patients with late relapse. The doublet treatment arm and the triplet arm each consisted of around one-third of patients with an early relapse, and around two-third of patients with a late relapse.
The median PFS was longer in patients who received the triplet combination than in those who received the doublet combination, regardless of early or late relapse. In patients with an early relapse, the median PFS was 24.7 months in those who received the triplet, while it was 17.2 months in those who received the doublet (hazard ratio [HR], 0.662; 95.4% CI, 0.404-1.087). In patients with a late relapse, the median PFS was 42.7 months in those who received the triplet, while it was 21.9 months in those who received the doublet (HR, 0.542; 95.4% CI, 0.353-0.833).
In patients with an early relapse, the overall response rates (ORR) were similar between those who received the triplet and those who received the doublet (82% vs 82.6%, respectively). The ORR in patients with late relapse who received the triplet was 90.4%, while it was 86.1% in those who received the doublet.
Overall, more patients who received the triplet than the doublet achieved a very good partial response or better (early relapse, 67.2% vs 52.2%, respectively; late relapse, 76.0% vs 58.3%), as well as minimal residual disease (MRD) negativity (early relapse, 24.6% vs 15.2%; late relapse, 37.5% vs 16.7%), and MRD negativity with complete remission (early relapse, 18.0% vs 10.9%; late relapse, 30.8% vs 13.9%).
The rate of grade 3 or higher and serious treatment-emergent adverse events were similar in both treatment arms for patients with any early relapse but were higher in the triplet treatment arm for patients with a late relapse. However, the rate of treatment-emergent adverse events that led to definitive discontinuation or death were similar in both treatment arms across patients with early and late relapses.
All-grade treatment-emergent adverse events including infusion reactions, upper respiratory tract infections, fatigue, dyspnea, bronchitis, cough, and gastroenteritis occurred more frequently in patients who received the triplet than in the doublet.
“The addition of [isatuximab to carfilzomib and dexamethasone] improved PFS and depth of response, with a manageable safety profile in both early and late relapse [patients], consistent with the benefit observed in the overall IKEMA study population,” the study’s authors concluded. “These results support [isatuximab plus carfilzomib and dexamethasone] as a standard of care in [patients] with relapsed and/or refractory [multiple myeloma] regardless of early or late relapse.”
Reference
Facon T, Moreau P, Baker R, et al. Isatuximab plus carfilzomib and dexamethasone in patients with early versus late relapsed multiple myeloma: IKEMA subgroup analysis. Abstract #753. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.
