Iberdomide, ixazomib and dexamethasone in elderly patients with multiple myeloma at first relapse

Abstract

Summary 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.