Multicenter phase 2 study of iberdomide with ixazomib and dexamethasone in elderly patients with multiple myeloma at first relapse

Most transplant-ineligible patients present with multiple myeloma (MM) refractory to lenalidomide and/or anti-CD38 monoclonal antibody at first relapse. A multicenter phase 2 trial in France evaluated the oral triplet iberdomide, ixazomib, and dexamethasone (I2D) in MM patients aged ≥ 70 years at first relapse. Median age was 76 years; 50% of patients were frail; 74% and 37% were refractory to lenalidomide and daratumumab, respectively. The median follow-up was 14 months. The overall response rate was 64%, including 36% very good partial response or better. The 12-month rates of progression-free survival, duration of response, and overall survival were 52%, 76%, and 86%, respectively. The most common grade 3 or 4 toxicity was neutropenia, in 46% of patients. Non-hematological adverse events were mostly grade 1 or 2. The authors conclude that I2D demonstrated a favorable risk-benefit profile in elderly MM patients at first relapse, including in patients with lenalidomide and daratumumab refractory disease.