Dr Gay on Efficacy Findings From the IsKia Trial in Multiple Myeloma

Francesca Gay, MD, PhD, associate professor, Department of Molecular Biotechnology and Health Sciences, the University of Torino, hematologist, the Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, discusses the safety and efficacy findings derivedfrom the phase 3 IsKia trial (NCT04483739) in patients with newly diagnosed multiple myeloma.

The IsKia trial, findings from which were presented at the 2023 ASH Annual Meeting, revealed that the combination of isatuximab-irfc (Sarclisa), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Isa-KRd) significantly increased minimal residual disease (MRD) negativity rates at the 10-5 and 10-6 cutoffs post-consolidation compared with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed patients. At a median follow-up of 21 months, MRD negativity rates at the 10-5 cutoff post-consolidation were 77% in the Isa-KRd arm (n = 151) vs 67% in the KRd arm (n = 151; OR, 1.67; P = .049). At the 10-6 cutoff, the MRD negativity rates were 67% and 48%, respectively (OR, 2.29; P < .001).

As such the trial’s primary end point, MRD negativity by next-generation sequencing after autologous stem cell transplant consolidation, was significantly higher with Isa-KRd vs KRd. Adverse effects (AEs), primarily hematological, were well managed in both arms. Subgroup analyses demonstrated consistent MRD negativity benefits with Isa-KRd vs KRd across risk groups.

Gay states that in the trial, Isa-KRD elicited a significantly higher rate of MRD negativity compared with KRd. This difference was evident at both the 10-5 and the 10-6 cutoffs, indicating a deep level of MRD negativity with Isa-KRd, she explains. Gay goes on to say that a key secondary end point of the study was the rate of MRD negativity after induction, which again favored Isa-KRd over KRd. At the 10-5 cutoff, the MRD negativity rates post-induction were 45% vs 26% in the Isa-KRd and KRd arms, respectively (OR, 2.34; P < .001), and at the 10-6 cutoff, these rates were 27% vs 14%, respectively (OR, 2.36; P = .004). MRD negativity rates improved over time after transplant and consolidation, Gay continues.

Approximately 40% of patients in the Isa-KRd arm and 30% of those in the KRd arm experienced grade 3/4 hematologic AEs, primarily neutropenia (36% vs 22%, respectively), she states. However, the infection rates were comparable between the 2 arms, Gay explains. Notably, there were no grade 3/4 neuropathy events, and the rate of cardiovascular toxicity was low, she concludes.