OA – 55: Iberdomide, daratumumab, and dexamethasone (IberDd) in transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM): results from the CC-220-MM-001 trial

Introduction: Lenalidomide (LEN), combined with daratumumab (DARA) and dexamethasone (DEX), is a standard of care for patients (pts) with TNE NDMM. The novel CELMoD™ agent iberdomide (IBER) is more potent than LEN in inducing conformational changes in cereblon, enabling more rapid degradation of Ikaros/Aiolos, thus enhancing myeloma cell death and immune stimulation. IBER has synergistic activity with DEX and DARA in preclinical models; IberDd has shown notable efficacy and tolerability in relapsed/refractory MM in the ongoing phase 1/2 CC-220-MM-001 trial (NCT02773030). Here we report the first results from the CC-220-MM-001 dose-expansion cohort of IberDd in TNE NDMM.


Methods: Eligible pts had untreated NDMM and no planned or recommended autologous stem cell transplant due to age/comorbidities. Oral IBER was given 1:1:1 at 3 doses (1.0, 1.3, and 1.6 mg) on days (D) 1–21 of each 28-day cycle (C) with subcutaneous DARA (1800 mg) on D1, 8, 15, and 22 in C1–2, on D1 and 15 in C3–6, and on D1 in ≥ C7, plus weekly oral DEX (40 mg; 20 mg if > 75 years of age). IBER doses were not modified based on renal impairment. Endpoints included preliminary efficacy, safety, and minimal residual disease (MRD) assessment.

Results: As of February 28, 2024, 75 pts received IberDd. Median age was 75 (range, 44–90) years, 42 (56.0%) pts were male, and 35 (46.7%) had creatinine clearance of 30 to < 60 mL/min. Extramedullary plasmacytomas were present in 6 (8.0%) pts and 31 (41.3%) pts had high-risk cytogenetics. Median follow-up was 11.14 (0.4–16.8) months. Median treatment duration was 10.7 (0.3–17.1) months, median number of cycles received was 12 (1–19), and 63 (84.0%) pts continued treatment; adverse events (AEs) were the most common cause of discontinuation (5.3%).

Grade (Gr) 3/4 treatment-emergent AEs (TEAEs) occurred in 70 (93.3%) pts; most were hematologic. Most common was neutropenia (74.7%); 9 (12.0%) pts had Gr 3 febrile neutropenia. Gr 3/4 infections occurred in 24 (32.0%) pts, including pneumonia (14 [18.7%] pts) and COVID-19 (4 [5.3%] pts). Most common non-hematologic Gr 3/4 TEAE was hyperglycemia (10.7%); other Gr 3/4 TEAEs were infrequent. IBER dose interruptions and reductions due to TEAEs occurred in 55 (73.3%) and 23 (30.7%) pts, respectively.

In the efficacy evaluable population (N = 73), overall response rate was 97.3% with 11 stringent complete responses, 22 complete responses (CRs), 29 very good partial responses (VGPRs), and 9 partial responses; 33 (45.2%) pts achieved ≥ CR and 62 (84.9%) pts ≥ VGPR. Median time to response was 1.0 (0.9–11.3) months; 76.1% of pts responded in < 6 weeks.

MRD negativity at 10^-5 was achieved in 28/62 (45.2%) pts at a response of ≥ VGPR.


Conclusions: In pts with TNE NDMM, preliminary data with IberDd showed high efficacy and a manageable safety profile with no new safety signals. Similar results were observed across dose levels. IberDd is being evaluated in an ongoing phase 3 trial in RRMM, and these data further support the evaluation of IBER in NDMM.