Iberdomide Maintenance after Autologous Stem-Cell Transplantation in Newly Diagnosed MM: First Results of the Phase 2 EMN26 Study

Background. Iberdomide is a novel oral cereblon E3 ligase modulator (CELMoD TM) with enhanced direct antitumor effects and immune stimulatory effects, compared to lenalidomide or pomalidomide. In the ongoing phase 1/2 CC-220-MM-001 study, iberdomide plus dexamethasone had a favorable safety profile and demonstrated clinically meaningful activity in triple-class refractory multiple myeloma (MM) patients, including those refractory to lenalidomide and pomalidomide (IMiDs ®). Based on these data, we aimed to evaluate the safety and clinical activity of 3 different doses of iberdomide as a novel maintenance treatment post-transplant in newly diagnosed MM patients. Here we report results from the first interim analysis for patients who have been treated with at least 6 treatment cycles, or discontinued treatment earlier. Methods. The EMN26 study is a multicohort, phase 2 study conducted in 4 European countries. Patients aged 18 years or older with MM, who had achieved at least a partial response (PR) after induction therapy containing a proteasome inhibitor (PI) plus IMiD followed by single or double autologous stem-cell transplantation (ASCT) +/- consolidation, were enrolled into one of 3 different cohorts (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 patients in each cohort). The primary outcome is improvement in response, and secondary outcomes include safety and progression-free survival (PFS). Response was evaluated at screening and after every cycle (bone marrow analysis was done at screening, at 6 and 12 months after treatment initiation, and to confirm (s)CR). This trial is ongoing and is registered with ClinicalTrials.gov (NCT04564703). Results. At data cut-off (May 31, 2023) 31 patients were enrolled in the 0.75 mg cohort, and 40 patients each in the 1.0 and 1.3 mg cohorts (total of 111). A total of 69 patients had received ≥6 cycles of iberdomide treatment or discontinued earlier (n=34 in 1.0 mg cohort; n=35 in 1.3 mg cohort; n=0 in 0.75 mg cohort [this cohort was added later]). Median age of these 69 patients was 59 years, and 57% were male. At diagnosis, 37% of patients presented with International Staging System (ISS) stage 1 disease, 35% with ISS stage 2, and 28% with stage 3. High-risk disease (del(17p), t(4;14), and/or t(14;16)) was present in 14% of patients. All patients received a PI/IMiD-containing induction regimen which also included daratumumab in 41