IsKia trial: results of Isa-KRd in transplant-eligible NDMM patients
Dr Annemiek Broijl, haematologist at the Erasmus MC hospital in Rotterdam, the Netherlands and co-principal investigator of the IsKia study was so kind to present the results. The study aims to assess the effectiveness of incorporating isatuximab into the standard treatment regimen of carfilzomib, lenalidomide and dexamethasone (KRd) during the pre-ASCT induction and post-ASCT consolidation phases in patients with NDMM. The induction and consolidation phases each comprised four cycles, followed by a 12-week maintenance phase with a reduced dose of Isa-KRd administered less frequently.
The data about the primary endpoints, specifically MRD negativity with NGS sensitivity set at 10-5 and 10-6, are presented.
The incorporation of isatuximab into the KRd regimen significantly enhanced MRD negativity at the 10-5 sensitivity level, with a rate of 77% compared to 67% in the control arm. This difference was more pronounced at a higher sensitivity of 10-6, where the Isa-KRd group demonstrated a rate of 67% compared to 48% in the control group.
Interestingly, this improvement was observed across all risk groups, including normal-risk patients, those with a single high-risk abnormality such as del(17p), t(14;16) or t(4;14), and higher-risk patients with two or more of these cytogenetic abnormalities or with gain(1q21) or amp(1q21). In all risk groups, MRD at the 10-5 level was comparable in patients receiving Isa-KRd, while a decline was noted in those on the KRd regimen. At the
10-6 sensitivity level, this trend was even more pronounced, with risk groups exhibiting a high MRD negativity ranging between 77-79% in the Isa-KRd arm. At each measured time point, including post-induction, post-high dose and post-consolidation, there was a 20% increase in MRD negativity.
The safety data from the combined treatment revealed minimal cardiotoxicity, with less than 5% incidence in both arms, addressing concerns related to carfilzomib. Peripheral neuropathy was notably low, and while neutropenia was observed, it was within the expected range.
While the results are encouraging for the Isa-KRd arm, the focus has been primarily on MRD negativity. Evaluation of the impact on PFS awaits further investigation. Initial PFS data after one year did not show any significant differences. Future research aims to establish sustained MRD results that translate into improved PFS outcomes for patients.
Reference:
Gay F,ASH2023. #4
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