Iberdomide, 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 and represent a difficult-to-treat population. The Intergroupe Francophone du Myélome phase 2 study iberdomide, ixazomib and dexamethasone (I2D) evaluated the oral triplet iberdomide, ixazomib and dexamethasone in MM patients aged ≥70 years at first relapse (NCT04998786). Seventy patients were enrolled to receive iberdomide (1.6 mg on day 1-21), ixazomib (3 mg on day 1, 8, 15) and dexamethasone (20 mg on day 1, 8, 15, 22 on cycle 1-2 and 10 mg on day 1, 8, 15, 22 on cycle 3-6) (28-day cycle) until disease progression. Median age was 76; 50% patients were frail according to the International Myeloma Working Group frailty score; 74% and 37% were refractory to lenalidomide and daratumumab respectively. With a median follow-up of 14 months, the overall response rate was 64%, including 36% very good partial response or better. The 12-month progression-free survival, duration of response and overall survival were 52%, 76% and 86% respectively. The most common (46%) grade 3-4 toxicity was neutropenia. Non-haematological adverse events were mostly grade 1 or 2. Overall, I2D demonstrated a favourable risk-benefit profile in elderly MM patients at first relapse, including in patients with lenalidomide and daratumumab refractory disease.