Iberdomide-Based Quadruplet Induction Followed by Maintenance Achieves High Response and MRD Negativity in NDMM

Quadruplet induction regimens which incorporate an anti-CD38 monoclonal antibody, proteasome inhibitor, immunomodulatory agent, and dexamethasone (Decadro) have become a standard approach for patients with newly diagnosed multiple myeloma (NDMM), yet efforts continue to optimize depth of response and durability while balancing tolerability.

Results from the phase 1/2 IDEAL study (NCT01682590) demonstrate that the novel regimen combining iberdomide, daratumumab (Darzalex; Janssen Biotech, Inc), bortezomib (Velcade; Millennium Pharmaceuticals), and dexamethasone (Iber-DVd) followed by iberdomide maintenance produced high response rates and encouraging minimal residual disease (MRD) negativity in both transplant-eligible and ineligible patients. These data were presented at the 2026 American Society of Clinical Oncology Annual Meeting.

A Next-Generation CELMoD–Based Quadruplet Strategy

Iberdomide is a cereblon E3 ligase modulator (CELMoD) designed with the intention of enhancing binding affinity and specificity compared with traditional immunomodulatory drugs, potentially improving antimyeloma activity. In the IDEAL study, the data evaluated a finite-duration induction strategy using Iber-DVd followed by iberdomide monotherapy maintenance in both transplant-eligible and transplant-ineligible patients with NDMM.

The dataset included a phase 1 dose-escalation component and a phase 2 expansion study, with the administration of iberdomide on days 1 through 21 of each 28-day cycle in combination with standard daratumumab, bortezomib, and dexamethasone. This follows 12 cycles of induction with patients progressing with iberdomide maintenance for up to 24 cycles.

High Response Rates Across Patient Populations

Among the 44 patients treated at the recommended phase 2 dose, the overall response rate was 100%, which demonstrated universal clinical activity of the regimen in this early analysis. Deep responses were also observed, with a ≥complete response (≥CR) rate of 36.4% during induction. This increased to approximately 52.3% overall with the addition of maintenance therapy.

Minimal residual disease (MRD) negativity further deepened over time. At a sensitivity threshold of 10^-5, MRD negativity was achieved in 29.5% of patients during induction and increased to 47.7% overall, highlighting ongoing treatment benefit with continued iberdomide exposure.

Responses were observed in a population with substantial baseline risk, including more than half of patients classified as high-risk disease.¹

Survival Outcomes and Early Durability

The median follow-up was about 18.3 months with early outcomes suggesting durable disease control. The 12- and 18-month progression-free survival rates were approximately 91% and 88%, respectively, whereas overall survival rates at the same time points were 97% and 94%.

Currently, follow-up remains limited, but these early survival estimates indicate promising disease control in a newly diagnosed population treated with a finite induction and maintenance strategy.

Safety Profile Consistent With Quadruplet Therapy

The Iber-DVd regimen demonstrated a safety profile consistent with known toxicities of multiagent myeloma therapy. The most common adverse effects included lymphopenia, neutropenia, rash, peripheral neuropathy, diarrhea, and infections. Approximately 27% of patients required pegfilgrastim support because of neutropenia.

High-grade fatigue was uncommon, and occurred in fewer than 5% of patients. No unexpected safety signals were reported, and toxicities were generally manageable with supportive care.

A Potential New CELMoD-Based Backbone in NDMM

The IDEAL study suggests that the incorporation of iberdomide into a quadruplet backbone may deepen responses and improve MRD negativity rates in both transplant-eligible and transplant-ineligible patients with NDMM. Notably, the responses continued to improve with maintenance therapy, resulting in nearly half of patients achieving MRD-negative status over time.

While longer follow-up is needed to confirm durability and survival benefit, these findings support further development of iberdomide-based regimens as a next-generation therapeutic strategy in newly diagnosed multiple myeloma.

REFERENCE

Kapoor P, Kumar S, Muchtar E, et al. Efficacy and safety of iberdomide, daratumumab, bortezomib, and dexamethasone in patients with newly diagnosed multiple myeloma. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29–June 2, 2026; Chicago, IL. Abstract 7514.