Lancet Haematol. 2026 Jan;13(1):e30-e40. doi: 10.1016/S2352-3026(25)00298-4.
ABSTRACT
BACKGROUND: Iberdomide is an oral cereblon E3 ligase modulator with higher affinity to cereblon than immunomodulatory drugs, leading to improved direct anti-myeloma activity and enhanced immunostimulatory effects. We aimed to evaluate the safety and activity of iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd) in patients with relapsed and refractory multiple myeloma.
METHODS: The ICON study is a prospective, single-arm, phase 2, open-label study conducted in eight hospitals in the Netherlands. We enrolled patients (aged ≥18 years) with relapsed and refractory multiple myeloma (lenalidomide-refractory) who had received two to four previous lines of therapy and had a WHO performance status of 0-2. Patients were treated with oral iberdomide (1·6 mg/day on days 1-21 of each 28-day cycle), oral low-dose cyclophosphamide (50 mg/day on days 1-28), and oral dexamethasone (40 mg [20 mg in patients age >75 years] once a week) until progression. All patients received thrombosis prophylaxis daily: 80 mg oral aspirin or 100 mg oral carbasalate calcium. Patients with a previous history of venous thromboembolism received only low molecular-weight heparin by subcutaneous injection. The primary endpoint was progression-free survival, defined as time from the start of treatment to the date of progression or death. Activity and safety were assessed in all patients who started treatment. This trial was registered at ClinicalTrials.gov (NCT04392037) and is ongoing.
FINDINGS: Between Feb 17, 2021, and July 7, 2023, 61 patients were enrolled and received IberCd treatment (29 [48%] were female and 32 [52%] patients were male). The median number of previous lines of therapy was 3 (range 2-5); 52 (85%) patients were triple-class exposed and 27 (44%) had triple-class refractory disease. 50 patients discontinued study treatment, 39 of whom due to progressive disease, but all 61 patients were included in the main analysis population. After a median follow-up of 25·4 months (IQR 19·7-31·6), the median progression-free survival was 17·6 months (one-sided 95% CI 16·6-19·9). In all 61 patients, the most common grade 3-4 adverse events were neutropenia (34 [56%] patients) and infections (21 [34%] patients). Treatment-related serious adverse events were reported in 25 (41%) patients, with infections being the most common (34 [71%] of 48 serious adverse events). Treatment-related death occurred in one (2%) patient due to COVID-19.
INTERPRETATION: IberCd is an all-oral and active combination for patients with relapsed and refractory multiple myeloma that showed clinically meaningful activity. This regimen offers a valuable treatment option for patients who have received two to four previous lines of therapy and compares favourably with other available treatments.
FUNDING: Bristol Myers Squibb.
PMID:41482445 | DOI:10.1016/S2352-3026(25)00298-4