Iberdomide vs Lenalidomide for Multiple Myeloma

Recruiting at 597 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must be taking: Proteasome inhibitors, Immunomodulatory drugs

Disqualifiers: Progressive disease, Smoldering myeloma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

1216 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, iberdomide (also known as CC-220, BMS 986382, or IBER) and lenalidomide (also known as Revlimid), to determine which is more effective for people with newly diagnosed multiple myeloma, a type of blood cancer. Participants have already undergone a stem cell transplant and some initial treatment. The study targets those who have shown at least some positive response to treatment and are still within about a year of starting therapy. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that iberdomide is generally safe when combined with other treatments for multiple myeloma. In one study, patients who had tried many other treatments found iberdomide to be safe. Another study confirmed that iberdomide was effective and safe when used with other medications.

Lenalidomide has been studied longer and is already approved for treating multiple myeloma. In a large study, some patients experienced reduced appetite, but few had significant weight loss or malnutrition. Lenalidomide is known to improve treatment response and extend patient survival when used with other treatments.

Both iberdomide and lenalidomide have been shown to be safe options for multiple myeloma, with lenalidomide having more long-term data available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about iberdomide for multiple myeloma because it represents a potential new approach in treating this cancer. Unlike traditional treatments such as lenalidomide, iberdomide is designed to modulate the immune system in a more targeted way, potentially leading to better outcomes with fewer side effects. Its unique mechanism of action, which involves modulating cereblon, a protein that plays a key role in the immune response, might offer improved effectiveness against resistant forms of multiple myeloma. This could make iberdomide a promising option for patients who have not responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will compare Iberdomide and Lenalidomide for treating multiple myeloma. Studies have shown that Iberdomide holds promise for treating this type of blood cancer. Research indicates that combining Iberdomide with other drugs, such as daratumumab and dexamethasone, has resulted in a high response rate of 93.1% in patients ineligible for transplants. Lenalidomide is also effective, with real-world data demonstrating its use in patients newly diagnosed with multiple myeloma. However, some studies found that Lenalidomide has a 55% response rate, with patients experiencing about 10 months without disease progression. This trial will compare these treatments to determine which might work better after stem cell transplants. ^{1 5 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for individuals with newly diagnosed symptomatic multiple myeloma who've had 3-6 cycles of specific induction therapies and a stem cell transplant within the last year, achieving at least partial response. It's not for those with progressive disease post-transplant, smoldering or nonsecretory myeloma, central nervous system involvement by MM, or other malignancies in the past 5 years.

Inclusion Criteria

I've had 3-6 cycles of specific cancer treatment and possibly a stem cell transplant.

I can take care of myself and am up and about more than half of my waking hours.

I have been diagnosed with symptomatic multiple myeloma.

Exclusion Criteria

My multiple myeloma has spread to my brain or spinal cord.

I have been cancer-free from other types of cancer for over 5 years.

My condition worsened after stem cell transplant or initial treatment didn't work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either iberdomide or lenalidomide maintenance therapy after autologous stem cell transplantation

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Iberdomide
• Lenalidomide

Trial Overview The study compares two maintenance therapies after autologous stem cell transplantation in new multiple myeloma patients: Iberdomide versus Lenalidomide. The goal is to see which one is more effective as a long-term treatment following initial therapy and transplant.

How Is the Trial Designed?

Group I: Arm A3: Iberdomide Dose 3 Experimental Treatment 1 Intervention

Group II: Arm A2: Iberdomide Dose 2 Experimental Treatment 1 Intervention

Group III: Arm A1: Iberdomide Dose 1 Experimental Treatment 1 Intervention

Group IV: Arm B: Lenalidomide Active Control 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Lenalidomide is a powerful treatment for multiple myeloma (MM) that works by directly causing cancer cell death, preventing cancer cells from sticking to bone marrow, and enhancing the body's immune response against tumors.

In combination with dexamethasone, lenalidomide has shown superior effectiveness in clinical trials, leading to improved patient outcomes such as longer survival and FDA approval for treating relapsed MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Hideshima, T., Raje, N., Richardson, PG., et al.[2021]

Immunomodulatory drugs like thalidomide and lenalidomide have shown significant effectiveness in treating multiple myeloma and related blood disorders, demonstrating high response rates across various treatment phases.

These drugs not only target cancer cells directly but also enhance the immune response within the bone marrow, and have been successfully combined with other treatments, leading to FDA approval for their use in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. Raje, N., Hideshima, T., Anderson, KC.[2018]

The combination therapy of lenalidomide, bendamustine, and prednisolone (RBP) showed a high response rate in 88% of the 25 patients with relapsed/refractory multiple myeloma, indicating its efficacy as a treatment option.

While RBP was effective, many patients experienced increased hematological toxicity, necessitating dose reductions in subsequent treatment cycles, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077). Beck, J., Schwarzer, A., Gläser, D., et al.[2018]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

Lenalidomide (REVLIMID®) is an effective treatment for multiple myeloma and transfusion-dependent anemia in myelodysplastic syndromes, showing better activity and less neurotoxicity compared to its predecessor, thalidomide.

This drug has multiple beneficial properties, including anti-inflammatory and antiangiogenic effects, and may play a significant role in treating various cancers beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of immunomodulatory drugs in the treatment of solid tumors. Dalgleish, A., Galustian, C.[2018]

Lenalidomide maintenance therapy significantly prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation, as shown in pivotal phase 3 trials like IFM 2005-02 and CALGB 100104.

While lenalidomide is associated with some increased risks, such as grade 3/4 adverse events and a higher chance of second primary cancers, the overall survival benefits outweigh these risks, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Newly Diagnosed Multiple Myeloma as Maintenance Therapy After ASCT. Syed, YY.[2018]

In a study of 184 patients with relapsed/refractory multiple myeloma, the generic lenalidomide (Rivelime®) showed similar efficacy to the brand-name version (Revlimid®) in terms of overall response rates and survival outcomes.

Both treatments resulted in comparable progression-free survival and overall survival rates, with manageable side effects, indicating that Rivelime® can be a safe and effective alternative to Revlimid® for long-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generic Lenalidomide Rivelime Versus Brand-name Revlimid® in the Treatment of Relapsed/Refractory Multiple Myeloma: A Retrospective Single-center Experience on Efficacy, Safety and Survival Outcome. Beksac, M., Seval, GC., Koyun, D., et al.[2023]

Citations

1. news.bms.com news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Phase-3-EXCALIBER-RRMM-Study-Evaluating-Iberdomide-in-Combination-with-Standard-Therapies-Demonstrated-a-Significant-Improvement-in-Minimal-Residual-Disease-Negativity-Rates-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx

Bristol Myers Squibb Announces Phase 3 EXCALIBER ... Stage 1 of the study identified 1.0 mg iberdomide as the optimal dose based on safety, pharmacokinetics, and efficacy data. In Stage 2, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04975997

NCT04975997 | Open-label Study Comparing Iberdomide, ... To evaluate clinical efficacy in terms of overall survival (OS) in participants with relapsed or refractory multiple myeloma (RRMM) treated with iberdomide, ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7532

Iberdomide, bortezomib, and dexamethasone (IberVd) in ... IberVd has shown meaningful efficacy and safety in patients (pts) with TNE NDMM in the ongoing phase 1/2 CC-220-MM-001 trial (NCT02773030).

4. onclive.com onclive.com/view/iberdomide-daratumumab-dexamethasone-is-effective-in-newly-diagnosed-multiple-myeloma

Iberdomide/Daratumumab/Dexamethasone Is Effective in ... The iberdomide-daratumumab-dexamethasone regimen achieved a 93.1% overall response rate in frail, transplant-ineligible multiple myeloma ...

5. healthtree.org healthtree.org/myeloma/community/articles/asco-25-iberdomide-for-older-mm-patients

Iberdomide Combo Effective in Older Myeloma Px Iberdomide Combination Shows Strong Results in Older Adults with Newly Diagnosed Myeloma. Some people with multiple myeloma are not eligible ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05560399

NCT05560399 | A Study of Iberdomide (CC-220) in ... This is a single-arm, open-label study evaluating the safety, tolerability and efficacy of Iberdomide (CC-220) in combination with Elotuzumab and Dexamethasone ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36209764/

Iberdomide plus dexamethasone in heavily pretreated late- ... Iberdomide plus dexamethasone was generally safe and showed meaningful clinical activity in heavily pretreated patients with multiple myeloma.

8. myeloma.org myeloma.org/treatment/multiple-myeloma-medications/iberdomide

Iberdomide How Is Iberdomide Used in Multiple Myeloma? While still in clinical trials, iberdomide has demonstrated some positive results. For example, combination therapy ...