Oral Iberdomide Combination Demonstrates Clinically Meaningful Activity for R/R Multiple Myeloma
Key Clinical Summary
- Population and Design: Phase 2, single-arm ICON trial evaluated oral iberdomide (1.6 mg d1–21 q28d) + low-dose cyclophosphamide (50 mg daily) + dexamethasone in 61 lenalidomide-refractory multiple myeloma patients (median 3 prior lines; 85% triple-class exposed, 44% triple-class refractory).
- Efficacy: At 25.4-month median follow-up, median progression-free survival (PFS) was 17.6 months (95% CI, 16.6 to 19.9), demonstrating clinically meaningful activity in a heavily pretreated population.
- Safety: Grade 3 to 4 adverse eventss: neutropenia (56%), infections (34%); serious AEs in 41% (mainly infections), including one treatment-related death (COVID-19).
- Clinical Relevance: The IberCd regimen provided a fully oral, active, and tolerable therapy for relapsed/refractory myeloma after multiple prior lines, offering a convenient and effective alternative that compares favorably to existing options.
The combination of iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd) demonstrated clinically meaningful activity and manageable toxicity in patients with relapsed/refractory (R/R) multiple myeloma (MM), according to results from the phase 2 ICON study published in The Lancet Haematology.
Previous research has found iberdomide, an oral cereblon E3 ligase modulator, to be associated with anti-myeloma activity and enhanced immunostimulatory effects. Researchers conducted a phase 2, single-arm, open-label trial to determine the safety and efficacy of iberdomide combined with low-dose cyclophosphamide and dexamethasone.
Eligible patients had received 2 to 4 prior lines of therapy and had a WHO performance status of 0 to 2. All patients received oral iberdomide (1.6 mg daily on days 1 to 21 of each 28-day cycle), cyclophosphamide (50 mg daily, continuous), and dexamethasone (40 mg weekly, reduced to 20 mg for patients over 75 years) until disease progression. Thrombosis prophylaxis was administered throughout.
The primary end point was progression-free survival (PFS), which was defined as time from treatment initiation to date of disease progression or death.
Overall, 61 patients with lenalidomide-refractory multiple myeloma were included. The median number of prior therapies was 3 (range, 2 to 5), and 85% of patients were triple-class exposed and 44% had triple-class refractory disease. The median PFS was 17.6 months (one-sided 95% confidence interval [CI], 16.6 to 19.9) at a median follow-up of 25.4 months (interquartile range [IQR], 19.7 to 31.6),
In terms of safety, the most common grade 3 or 4 adverse events were neutropenia (56%) and infections (34%). Treatment-related serious adverse events occurred in 41% of patients, of which most were infections (71%). One treatment-related death due to COVID-19 was reported.
The researchers concluded, “IberCd is an all-oral and active combination for patients with relapsed and refractory multiple myeloma that showed clinically meaningful activity.”
They added, “This regimen offers a valuable treatment option for patients who have received 2 to 4 previous lines of therapy and compares favourably with other available treatments.”
Source:
Korst CLBM, Plattel W, de Kort EA, et al. Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial. The Lancet Haematology. Published online January 2026. doi:10.1016/s2352-3026(25)00298-4
