Iberdomide + Dexamethasone for Smoldering Multiple Myeloma

Overseen By Nisha S. Joseph, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Zidovudine, Stavudine

Disqualifiers: Multiple myeloma, MGUS, Hepatitis B, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effects of iberdomide when given alone or in combination with dexamethasone in treating intermediate or high-risk smoldering multiple myeloma patients. Immunotherapy with iberdomide may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Dexamethasone is a synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland), and is used with other drugs in the treatment of some types of cancer. Giving iberdomide with dexamethasone my improve time to progression to symptomatic myeloma with improved tolerability.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial, except for certain low-dose steroids and specific types of steroid applications.

What evidence supports the effectiveness of the drug combination Iberdomide and Dexamethasone for treating smoldering multiple myeloma?

Iberdomide, when combined with dexamethasone, has shown promising results in preclinical models of multiple myeloma, demonstrating enhanced tumor-killing and immune-boosting effects. Additionally, similar drug combinations like pomalidomide plus dexamethasone have been effective in treating relapsed or refractory multiple myeloma, suggesting potential benefits for Iberdomide and Dexamethasone in smoldering multiple myeloma. ^{1 2 3 4 5}

Is Iberdomide plus Dexamethasone safe for humans?

In a study of Iberdomide plus Dexamethasone for multiple myeloma, the treatment was evaluated for safety, but specific side effects were not detailed in the provided abstract. However, similar treatments with Dexamethasone have reported side effects like fatigue, muscle cramps, and infections. ^{1 6 7 8 9}

What makes the drug Iberdomide + Dexamethasone unique for treating smoldering multiple myeloma?

Iberdomide is a new type of drug that works by enhancing the body's immune response and killing cancer cells more effectively than older drugs. It shows a strong synergy (works well together) with dexamethasone, making it a promising option for patients with smoldering multiple myeloma, especially since there are limited standard treatments for this condition. ^{1 2 10 11 12}

Research Team

Nisha S Joseph, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for people with a condition called smoldering multiple myeloma, who haven't had treatment yet. They need to have certain blood and liver function levels, be diagnosed within the last 5 years, and not have other health issues that could affect the trial. Women who can get pregnant must follow strict rules about testing and birth control.

Inclusion Criteria

I am willing to follow the study's fertility guidelines.

Subject is willing and able to adhere to the study visit schedule and other protocol requirements

I have another cancer type, but it won't affect this trial's treatment.

Exclusion Criteria

I use bisphosphonates through IV more than once a year.

There are specific rules for people with HIV.

I am receiving or have received treatment for a plasma cell disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iberdomide hydrochloride with or without dexamethasone. Treatment repeats every 28 days for 4 cycles in Arm A, followed by iberdomide alone. Arm B receives iberdomide alone.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Initial follow-up is 4 weeks, then every 6 months.

4 weeks initial, then every 6 months

Treatment Details

Interventions

• Dexamethasone
• Iberdomide Hydrochloride

Trial Overview The study is looking at how well a drug called Iberdomide works on its own or when combined with Dexamethasone in patients with intermediate or high-risk smoldering multiple myeloma. It's checking if this combo can delay the disease from getting worse while being easier to tolerate.

Participant Groups

Group I: Arm A (iberdomide hydrochloride, dexamethasone) Experimental Treatment 3 Interventions

Patients receive iberdomide hydrochloride PO QD on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (iberdomide hydrochloride) Active Control 3 Interventions

Patients receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Bristol-Myers Squibb

Industry 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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In two cases of multiple myeloma resistant to conventional therapies, patients showed significant improvement after treatment with bortezomib and dexamethasone, with one patient experiencing a decrease in serum IgG from 8040 to 1020 mg/dl and another from 2140 to 623 mg/dl.

The combination therapy not only proved effective in reducing tumor markers but also resulted in milder adverse reactions when dexamethasone was added, suggesting it may help mitigate side effects associated with bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. Ikeda, H., Hayashi, T., Nojima, M., et al.[2015]

In a real-world study involving 151 patients with relapsed or refractory multiple myeloma, the combination of pomalidomide and low-dose dexamethasone (POM/DEX) demonstrated a median progression-free survival of 6.3 months and overall survival of 12.9 months, indicating its effectiveness in this patient population.

The treatment was generally safe, with the most common severe side effects being leukopenia (8.2%), pneumonia (7.5%), and anemia (5.5%), while patients maintained their quality of life after starting POM/DEX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials. Dechow, T., Aldaoud, A., Behlendorf, T., et al.[2022]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

The BLT-D regimen, which combines clarithromycin, low-dose thalidomide, and dexamethasone, showed a high response rate of 93% in 50 patients with multiple myeloma, indicating its efficacy as a treatment option.

While the treatment was generally well-tolerated, neurotoxicity was the main reason for discontinuation, and caution is advised for patients with existing health issues like severe cardiopulmonary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. Coleman, M., Leonard, J., Lyons, L., et al.[2022]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

In a pooled analysis of 1088 heavily pretreated patients with relapsed and refractory multiple myeloma, pomalidomide combined with low-dose dexamethasone demonstrated an acceptable safety profile, with the most common severe adverse events being neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%).

Adverse events were effectively managed through dose modifications and supportive care, with 24.2% of patients requiring dose reductions and 66.0% experiencing treatment interruptions, indicating that while side effects were significant, they were manageable to allow continued therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Moreau, P., Dimopoulos, MA., Richardson, PG., et al.[2018]

In a study of 30 patients with double-relapsed/refractory multiple myeloma, the combination treatment of bendamustine, thalidomide, and dexamethasone (BTD) resulted in 87% of patients achieving stable disease or better, indicating significant efficacy as a salvage treatment.

The median progression-free survival was 4.0 months and overall survival was 7.2 months, with common adverse effects being hematological, such as neutropenia and anemia, suggesting that while BTD is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide. Lau, IJ., Smith, D., Aitchison, R., et al.[2018]

In a study involving bone marrow plasma cells from 39 multiple myeloma patients, both interferon-gamma (IFN-gamma) and dexamethasone (DEX) significantly inhibited cell proliferation and immunoglobulin secretion, indicating their potential as effective anti-tumor agents.

The combination of IFN-alpha and IFN-gamma, while not showing additive effects, still resulted in strong inhibition of both cell proliferation and immunoglobulin secretion, suggesting that their different mechanisms of action could be explored for new treatment strategies in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells. Palumbo, A., Battaglio, S., Napoli, P., et al.[2019]

A 70-year-old man with indolent myeloma showed significant clinical improvement after treatment with high-dose dexamethasone, despite presenting with unusual symptoms and no bone pain.

This case highlights the potential efficacy of high-dose dexamethasone in managing atypical presentations of multiple myeloma, particularly in patients who may not exhibit common symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A smoldering/indolent myeloma with extensive abdominal presentation--case report. Omoti, CE., Enosolease, ME.[2013]

References

1. England 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. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells. [2019]

12. India pubmed.ncbi.nlm.nih.gov

A smoldering/indolent myeloma with extensive abdominal presentation--case report. [2013]