Dr Lonial on Data for Iberdomide Plus Daratumumab/Dexamethasone in Newly Diagnosed Myeloma

“As we think about cohort K [of the CC-220-MM-001 trial], which [evaluated] iberdomide, daratumumab, and dexamethasone for transplant-ineligible patients, there really were a couple of take-home messages. The first relates to the depth of response. The complete remission rate was roughly double what we saw with the MAIA trial.”

Sagar Lonial, MD, FACP, FASCO, professor and chair of the Department of Hematology and Medical Oncology, and the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, as well as the chief medical officer at Winship Cancer Institute of Emory University, outlined emerging data supporting CELMoD-based combination approaches for patients with multiple myeloma.

In a presentation at the 22nd Annual International Myeloma Society Meeting and Exposition in 2025, Lonial highlighted findings from the phase 1/2 CC-220-MM-001 study (NCT02773030) evaluating iberdomide (CC-220) in combination regimens across newly diagnosed and relapsed/refractory multiple myeloma settings, including cohort K where patients with newly diagnosed, transplant-ineligible or -defered multiple myeloma were treated with iberdomide plus daratumumab (Darzalex) and dexamethasone.

Findings from cohort K showed that evaluable patients with newly diagnosed, transplant-ineligible or -deferred multiple myeloma treated with the triplet (n = 75) achieved an overall response rate (ORR) of 94.7%, including a complete response (CR) or better rate of 68.0%, a stringent CR rate of 29.3%, and a very good partial response or better rate of 88.0%. Notably, the 68.0% CR or better rate represented an improvement on the CR rate or better rate reported with -long-term outcomes from the phase 3 MAIA trial (NCT02252172) that evalauted daratumumab plus lenalidomide (Revlimid) and dexamethasone in patients with newly diagnosed, transplant-ineligible multiple myeloma. This CR or better rate reported in cohort K of CC-220-MM-001 was supplemented by deep molecular responses, Lonial said. The minimal residual disease (MRD)–negativity rate was 64.0% at a sensitivity of 10^-5 among the overall population; in those who achieved a CR or better, the MRD-negativity rate was 56.0%. The median duration of response was not reached (NR; 95% CI, NR-NR).

Importantly, Lonial underscored that in transplant-ineligible or frail patients who are often treated continuously, achieving deeper and potentially more durable remissions without escalating toxicity is a central therapeutic goal.

Safety findings from cohort K further reinforced the potential value of CELMoDs in this setting. Lonial noted that adverse effects were lower than what is typically observed with lenalidomide-based therapy, an important consideration in older or medically vulnerable patients. Class-associated toxicities commonly seen with immunomodulatory drugs (IMiDs) were reported less frequently with iberdomide. He framed this as a potential distinguishing feature of CELMoDs, which may offer greater potency with improved tolerability compared with earlier-generation IMiDs.

Collectively, Lonial concluded that the iberdomide, daratumumab, and dexamethasone combination demonstrated a favorable balance of efficacy, depth of response, and tolerability in patients with transplant-ineligible newly diagnosed multiple myeloma. Although longer follow-up is needed to confirm durability and survival outcomes, these data support continued development of CELMoD-based regimens as a foundation for frontline therapy in this population.