IsKia: Novel treatment regimen for MM delivers high MRD-negativity rates

Isatuximab (Isa) plus carfilzomib, lenalidomide, and dexamethasone (KRd) as pre-transplant induction and post-transplant consolidation therapy increased MRD negativity rates compared with KRd alone in participants with previously untreated multiple myeloma (MM).

A total of 302 participants with newly diagnosed MM were randomised 1:1 to Isa-KRd or KRd alone in the phase 3 IsKia trial (NCT04483739). Participants in the experimental arm received 4x 28-day cycles of Isa-KRd induction therapy, followed by chemotherapy and autologous stem cell transplantation (autoSCT). Thereafter, participants received another set of 4x 28-day cycles of Isa-KRd consolidation therapy. The regimen in the control arm was analogous, except with the omission of isatuximab. The primary endpoint was MRD negativity by next-generation sequencing after post-autoSCT consolidation therapy. Prof. Francesca Gay (University of Torino, Italy) presented the primary results [1].

The primary endpoint was met, with MRD negativity rates at the 10^-6 level of 67% and 48%, in favour of the experimental arm (OR 2.29; P<0.001). Prof. Gay showed that MRD-negativity rates improved over time, from 27% post-induction to 52% post-autoSCT and 67% post-consolidation in the experimental arm. Corresponding rates in the control arm were 14%, 27%, and 48%. Interestingly, post-consolidation MRD negativity rates among participants with very high-risk disease were consistent in the experimental arm but were reduced in the control arm (77% vs 27%). At the current follow-up (median 20 months), there was no difference in progression-free survival (95% at 1 year in both arms).

The safety profiles of the 2 regimens were comparable. Yet, grade 3–4 neutropenia was more common in the experimental arm (36% vs 22%; P=0.008).

“Isa-KRd significantly increased MRD negativity after induction, transplantation, and consolidation therapy in participants with newly diagnosed MM,” concluded Dr Gay. “1-year sustained MRD rates will become available in 2024.”

1. Gay F, et al. Results of the phase III randomised IsKia trial: isatuximab-carfilzomib-lenalidomide-dexamethasone vs carfilzomib-lenalidomide-dexamethasone as pre-transplant induction and post-transplant consolidation in newly diagnosed multiple myeloma patients. Plenary session Abstract 4. 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

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Posted on 7 February 202415 February 2024