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    Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    (OA-50) Iberdomide, Daratumumab, and Dexamethasone (IberDd) in Transplant-Ineligible/Deferred (TNE) Newly Diagnosed Multiple Myeloma (NDMM): Updated Results from the CC-220-MM-001 Trial

    Saturday, September 20, 2025
    08:00 - 08:10 East Coast USA Time
    Location: Room 701

      Abstract Presenter(s)

    • Sagar Lonial, MD, FACP

      Professor and Chair
      Emory University School of Medicine, Atlanta, GA, USA
      Atlanta, Georgia

    Introduction: Lenalidomide (LEN) plus daratumumab (DARA) and dexamethasone (DEX) is a standard-of-care treatment for TNE NDMM. Iberdomide (IBER) is an oral CELMoD™ agent with greater potency than LEN; it binds cereblon with higher affinity, leading to more efficient cereblon conformational changes resulting in faster and greater Ikaros/Aiolos degradation and enhanced tumoricidal and immunostimulatory activity. Efficacy and tolerability of IberDd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) have been shown in the ongoing phase 1/2 CC-220-MM-001 trial (NCT02773030). IberDd also showed high efficacy and a manageable safety profile across dose levels in a cohort of pts with TNE NDMM. Here we report an updated analysis of this pt population with extended follow-up.

    Methods:

    Eligible pts were adults with untreated NDMM and with no planned or were ineligible for autologous stem cell transplant. Pts were randomized 1:1:1 to receive oral IBER doses of 1.0, 1.3, or 1.6mg on days (D) 1–21 of each 28-day cycle (C) combined with DARA (1800mg) on D1, 8, 15, and 22 in C1–2, on D1 and 15 in C3–6, and on D1 in ≥C7, plus weekly DEX (40mg; 20mg if >75 years of age). Efficacy, safety, and minimal residual disease (MRD) were assessed.

    Results:

    As of March 3, 2025, 75 pts in this cohort received IberDd. Of these, 44 (58.7%) were aged ≥75 years and 31 (41.3%) had high-risk cytogenetics. Median follow-up was 22.3 (range, 0.4–28.5) months and 50 (66.7%) pts remained on therapy; pts discontinued due to adverse events (AEs) (9 [12.0%] pts), progressive disease (7 [9.3%] pts), pt withdrawal (4 [5.3%] pts), death (3 [4.0%] pts), and physician decision (2 [2.7%] pts). Median treatment duration was 22.3 (range, 0.3–29.0) months.

    Safety data were consistent with the primary analysis. Grade (Gr) 3/4 treatment-emergent AEs (TEAEs) were observed in 73 (97.3%) pts; Gr 3/4 hematologic TEAEs were observed in 63 (84.0%) pts, with neutropenia being the most common (78.7%). Excluding infections (52.0%), non-hematologic Gr 3/4 events were infrequent.

    The overall response rate was 94.7%. Since the primary analysis, pts sustained durable responses that deepened over time; complete response (CR) or better was observed in 51 (68.0%) pts and very good partial responses were observed in 15 (20.0%) pts. Median time to response for responders was 4.1 (range, 4.0–49.0) weeks. Median duration of response and median progression-free survival were not reached. Overall, 64.0% (48/75) pts achieved MRD negativity, and 56.0% (42/75) pts achieved MRD-negative CR (10-5 threshold) in the intention-to-treat population.

    Conclusions: With additional follow-up, IberDd continued to show high efficacy and a manageable safety profile with no new safety signals in TNE NDMM. Pts experienced durable responses that deepened over time. These data support further evaluation of IberDd in NDMM. IberDd is also being investigated in the ongoing phase 3 EXCALIBER-RRMM (NCT04975997) trial.