August 2023

Katie Robinson

In patients with early relapsed multiple myeloma (MM), the addition of the anti-CD38 antibody isatuximab (Isa) to carfilzomib-dexamethasone (Kd) maintained the improved progression-free survival (PFS) reported in interim results of the phase III IKEMA study, according to a longer-term analysis of the study published in Blood Cancer Journal.¹

“Isa-Kd is a very active regimen in patients with early relapsed MM, reporting a PFS of close to three years, one of the best results reported in these patients,” said lead author Thomas Martin, MD, of the University of California, San Francisco Medical Center. “Additionally, we reported one of the highest rates of complete response (CR) and CR with MRD [measurable residual disease] negativity.”

Isa-Kd was approved for use in patients with relapsed or refractory (R/R) MM based on the results of the interim analysis of the phase III IKEMA study, in which the addition of Isa to Kd improved PFS after one to three prior lines of therapy.²

In this 44-month follow-up analysis of the IKEMA study, the longer-term outcomes of Isa-Kd were evaluated. The primary endpoint was PFS. The study also assessed final CR, MRD negativity, and safety. The CR rate was the proportion of patients achieving a stringent CR or CR as best overall response according to criteria from the International Myeloma Working Group. Of the patients with R/R MM with one to three prior treatment lines, 179 patients (median age = 65) were randomly assigned to treatment with Isa-Kd, and 123 patients (median age = 63) were randomly assigned to Kd alone. About a quarter of the patients in each treatment arm (23.5% in the Isa-Kd arm and 25.2% in the Kd arm, respectively) had high-risk cytogenetic status.

As seen in the interim analysis, the addition of Isa to Kd prolonged the PFS (hazard ratio [HR] = 0.58; 95.4% CI 0.42-0.79), corresponding to a 42% reduction in the risk of progression or death with Isa-Kd versus Kd. The median PFS was 35.7 months [95% CI 25.8-44.0] for Isa-Kd and 19.2 months [95% CI 15.8-25.0] for Kd. The PFS benefit with Isa-Kd was seen across subgroups, including patients with poor prognosis, such as older patients, those with renal function impairment, patients with high-risk cytogenetics, and patients who were refractory to lenalidomide. For Isa-Kd and Kd, the stringent CR/CR rates were 44.1% and 28.5%, respectively (odds ratio [OR] = 2.09; 95% CI 1.26-3.48), the MRD negativity rates were 33.5% and 15.4%, respectively (OR=2.78; 95% CI 1.55-4.99), and the MRD negativity CR rates were 26.3% and 12.2%, respectively (OR=2.57; 95% CI 1.35-4.88).

Isa-Kd showed a similar safety profile to that reported in the interim analysis. The addition of Isa to Kd did not increase the incidence of treatment emergent adverse events (TEAEs) with fatal outcome during treatment or TEAEs leading to treatment discontinuation. The researchers noted that higher incidence of any-grade serious TEAEs in Isa-Kd compared with Kd was related to the longer treatment exposure. The median duration of treatment with Isa-Kd was 94 weeks versus 61.9 weeks with Kd. As with the interim analysis, the most frequent TEAEs were infusion reactions, diarrhea, hypertension, and upper respiratory tract infections, mostly of grade 1-2.

“All subgroups of patients seemed to benefit from Isa-Kd, including older age, high risk, and those with renal insufficiency. The regimen was also well tolerated, even in patients older than 70,” Dr. Martin said. “Isa-Kd should be considered as a standard regimen for the treatment of patients with early relapsed (one to three prior treatment lines) MM.”