IBERDOMIDE combination therapy has demonstrated clinically meaningful activity in relapsed and refractory multiple myeloma, with a median progression free survival of nearly 18 months in a phase 2 study population with substantial prior treatment exposure.
Study Background and Rationale
Relapsed and refractory multiple myeloma remains challenging to manage, particularly in patients who are refractory to lenalidomide and have received multiple previous lines of therapy. Iberdomide is an oral cereblon E3 ligase modulator with higher affinity to cereblon than existing immunomodulatory drugs, resulting in enhanced direct anti myeloma activity and immunostimulatory effects. The ICON study evaluated the safety and activity of iberdomide combined with low dose cyclophosphamide and dexamethasone, referred to as IberCd, in this difficult to treat population.
ICON Study Design and Population
ICON is a prospective, single arm, phase 2, open label study conducted across eight hospitals in the Netherlands. Patients aged 18 years or older with relapsed and refractory multiple myeloma who had received two to four previous lines of therapy and had a World Health Organization performance status of 0–2 were enrolled. All participants were refractory to lenalidomide. Treatment consisted of oral iberdomide 1.6 mg on days 1–21 of each 28 day cycle, continuous low dose oral cyclophosphamide, and weekly oral dexamethasone. Thrombosis prophylaxis was mandatory for all patients. The primary endpoint was progression free survival, defined as time from treatment initiation to disease progression or death.
Efficacy and Safety Outcomes
Between February 2021 and July 2023, 61 patients initiated IberCd therapy and were included in the main analysis. The median number of previous treatment lines was three, with 85% of patients being triple class exposed and 44% having triple class refractory disease. After a median follow up of 25.4 months, median progression free survival was 17.6 months: one sided 95% CI: 16.6–19.9. With regard to safety, the most common grade 3–4 adverse events were neutropenia and infections. Treatment related serious adverse events occurred in 41% of patients, most frequently infections. One treatment related death due to COVID 19 was reported.
These data indicate that IberCd is an all oral and active treatment option for patients with relapsed and refractory multiple myeloma who have received two to four prior therapies.
Reference
Korst CLBM 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. Lancet Hematol. 2026;13:1:E30-40.
