KEY TAKEAWAYS
- The EMN26 phase 2 trial aimed to investigate the safety and clinical activity of 3 different doses of iberdomide in newly diagnosed MM pts.
- The primary outcome was improvement in response, and the secondary outcomes were safety and PFS.
- Researchers noticed superior response improvement at 6 months with iberdomide post-ASCT maintenance compared to lenalidomide. Additional follow-up is needed for the study.
Iberdomide, a novel oral cereblon E3 ligase modulator (CELMoDTM), has demonstrated enhanced direct antitumor and immune stimulatory effects compared to lenalidomide or pomalidomide. In the phase 1/2 CC-220-MM-001 study, the combination of iberdomide and dexamethasone exhibited a favorable safety profile and clinically meaningful activity in triple-class refractory multiple myeloma (MM) patients (pts), including those resistant to lenalidomide and pomalidomide (IMiDs®).
Niels W.C.J. van de Donk and his team aimed to assess the safety and clinical activity of iberdomide as a novel maintenance treatment post-transplant in newly diagnosed MM pts. The first interim analysis reports results for pts who underwent at least 6 treatment cycles or discontinued treatment earlier, providing insights on the early outcomes of iberdomide as a post-transplant maintenance strategy.
Researchers conducted an inclusive analysis as part of the multicohort, phase 2 EMN26 study spanning 4 European countries. Eligible pts, aged 18 or older with MM, achieving at least a partial response (PR) post-induction therapy, including a proteasome inhibitor (PI) plus immunomodulatory drug (IMiD) followed by single or double autologous stem-cell transplantation (ASCT) +/- consolidation, were enrolled in one of 3 cohorts. Each cohort received varying doses of (iberdomide 0.75, 1.0, or 1.3 mg on days 1-21 of each 28-day cycle; treatment continued until progression or unacceptable toxicity; 40 pts in each cohort).
The primary outcome focused on response improvement, while secondary outcomes encompassed safety and progression-free survival (PFS). Response evaluation occurred at screening and after each cycle (bone marrow analysis was done at screening, at 6 and 12 months after treatment initiation, and to confirm (s) CR). This ongoing trial provided valuable insights into the efficacy and safety of iberdomide in MM pts post-ASCT, guiding further understanding of its clinical impact.
About 31 pts were enrolled in the 0.75 mg cohort, and 40 pts each in the 1.0 and 1.3 mg cohorts, comprising 111 participants on May 31, 2023. Among them, 69 pts received ≥6 cycles of iberdomide treatment or discontinued earlier (n=34 in the 1.0 mg cohort; n=35 in the 1.3 mg cohort; n=0 in the 0.75 mg cohort, added later). The median age of these 69 pts was 59 years, with 57% being male.
At the time of diagnosis, 37% of pts presented with International Staging System (ISS) stage 1 disease, 35% with ISS stage 2, and 28% with stage 3. High-risk disease, characterized by del(17p), t(4;14), and/or t(14;16), was observed in 14% of pts. All pts had received a proteasome inhibitor (PI)/immunomodulatory drug (IMiD)-containing induction regimen, with daratumumab included in 41% of cases. Double ASCT was administered to 19%, and post-ASCT consolidation to 7%.
The best response at the time of study enrollment varied, with the 1.0 mg cohort showing PR in 15%, very good partial response (VGPR) in 59%, complete response (CR) in 12%, and stringent complete response (sCR) in 15% (≥CR: 26%). In the 1.3 mg cohort, PR was observed in 3%, VGPR in 69%, CR in 11%, and sCR in 17% (≥CR: 29%).
After 6 treatment cycles, a comparable deepening of response was noted in both cohorts. In the 1.0 mg cohort, PR was 6%, VGPR 44%, CR 3%, and sCR 47% (≥CR: 50%), while in the 1.3 mg cohort, PR was 3%, VGPR 37%, CR 9%, and sCR 51% (≥CR: 60%). A notable improvement in response was reported in 48% of pts treated with 1.0 mg iberdomide and 45% in the 1.3 mg cohort, significantly surpassing the null hypothesis of ≤20% response improvement within 6 months.
The most common grade 3 or worse adverse events (AEs) during cycles 1-6 included neutropenia (21% in the 1.0 mg cohort and 46% in the 1.3 mg cohort), infections (3% and 14%), and fatigue/asthenia (12% and 14%). No events of ≥grade 3 thrombocytopenia, anemia, diarrhea, venous thromboembolism (VTE), or neuropathy were reported. Dose reductions were implemented in 18% of pts in the 1.0 mg cohort and 31% in the 1.3 mg cohort to manage AEs. Treatment discontinuation occurred in 3 pts in the 1.0 mg cohort (1 due to AE, 2 due to progressive disease [PD]), and 4 pts in the 1.3 mg cohort (2 due to AE, 1 due to PD, and 1 due to an unknown cause).
Progression-free survival (PFS) at 6 months was 97% in the 1.0 mg cohort and 94% in the 1.3 mg cohort. Further details, including results from the 0.75 mg cohort and minimal residual disease (MRD) conversion data, will be presented with longer follow-up.
The study concluded that iberdomide is a promising post-ASCT maintenance strategy, exhibiting a favorable safety profile and superior response improvement at 6 months compared to lenalidomide maintenance (26% at 6 months in the EMN02 study). However, further follow-up is essential to determine the recommended maintenance dose. The upcoming randomized phase 3 EXCALIBER maintenance study, comparing iberdomide to lenalidomide post-ASCT, will provide critical insights for optimizing this novel maintenance approach in MM pts.
The study is sponsored by Stichting European Myeloma Network
Source: https://ash.confex.com/ash/2023/webprogram/Paper177564.html
Clinical Trial: https://clinicaltrials.gov/study/NCT04564703
Donk N W.C.J V D, Touzeau C, Terpos E, et al. (2023). ” berdomide Maintenance after Autologous Stem-Cell Transplantation in Newly Diagnosed MM: First Results of the Phase 2 EMN26 Study” Presented at ASH 2023 (Abstract 208).
