Multicenter phase 2 trial of iberdomide plus low-dose cyclophosphamide and dexamethasone for relapsed or refractory multiple myeloma

Iberdomide is an oral cereblon E3 ligase modulator with higher affinity to cereblon than immunomodulatory drugs. The phase 2 ICON study, at eight hospitals in The Netherlands, evaluated iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd) for relapsed and refractory multiple myeloma (RRMM, lenalidomide-refractory), who had received two to four previous lines of therapy and had a WHO performance status of 0-2. All patients received thrombosis prophylaxis daily (aspirin or carbasalate calcium). Patients with a history of venous thromboembolism received only low-molecular weight heparin. Among 61 enrolled patients, the median number of previous line of therapy was 3; 85% were triple-class exposed, and 44% had triple-class refractory disease. At a median follow-up of 25.4 months (IQR 19.7-31.6), the median progression-free survival was 17.6 months (95% CI 16.6-19.9). The most common grade 3 or 4 adverse events were neutropenia (56%) and infections (34%). Treatment-related serious adverse events were reported for 41%. Treatment-related death occurred in one patient. The authors conclude that IberCd is an all-oral and active combination for patients with RRMM.