Immunotherapy for Smoldering Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Chemotherapy, Immunosuppressants, others

Disqualifiers: Myeloma, Autoimmune, HIV, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 72 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot early phase I trial studies pembrolizumab in treating patients with slow growing (smoldering) multiple myeloma with intermediate or high-risk of spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does not allow certain treatments like corticosteroids, radiotherapy, or chemotherapy for smoldering multiple myeloma. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab (KEYTRUDA, MK-3475) for smoldering multiple myeloma?

In a pilot study, pembrolizumab showed potential in preventing the progression of smoldering myeloma in a subset of patients, with one patient achieving a complete response and most others maintaining stable disease. Additionally, pembrolizumab has shown effectiveness in other forms of multiple myeloma, with some patients experiencing significant responses and prolonged progression-free survival. ^{1 2 3 4 5}

Is pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (Keytruda) has been used in various cancer treatments and is generally considered safe, but it can cause some immune-related side effects. These include rare cases of type 1 diabetes, pneumonitis (lung inflammation), and other immune system reactions. Most side effects are manageable, but some can be serious, so monitoring by healthcare professionals is important. ^{2 4 6 7 8}

How is the drug pembrolizumab unique for treating smoldering multiple myeloma?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells. This approach is different from traditional treatments, as it aims to enhance the body's own immune response to prevent the progression of smoldering multiple myeloma. ^{1 2 3 5 9}

Research Team

Elisabet E Manasanch, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with intermediate or high-risk smoldering multiple myeloma who meet specific diagnostic criteria, have good kidney function and general health, and can give informed consent. They must not have active autoimmune diseases, other cancers, severe lung conditions, infections needing systemic therapy, or a history of certain immune disorders.

Inclusion Criteria

Adults with a certain type of smoldering multiple myeloma that is at intermediate or high risk.

Your SMM diagnosis is confirmed by specific medical criteria from the Mayo clinic, PETHEMA, or SWOG.

Your kidneys work well enough to filter out waste from your blood.

Exclusion Criteria

You have had a serious autoimmune disease that needed strong medication in the last 2 years.

You have another cancer that is currently getting worse or is still active.

You have a history of needing steroids for lung inflammation or currently have lung inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 24 courses

72 weeks

24 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

Follow-up every 6-12 months

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The trial is testing pembrolizumab's effectiveness for patients with slow-growing multiple myeloma at risk of spreading. It's an early phase study to see how well the body's immune system can fight cancer when helped by this monoclonal antibody drug.

Participant Groups

Group I: Treatment (pembrolizumab) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The introduction of new therapies, including proteasome inhibitors, immunomodulators, and various immunotherapies like CAR T-cell treatments, has significantly improved the five-year survival rate for multiple myeloma to nearly 60%.

Despite these advancements, multiple myeloma remains incurable, as patients often become resistant to treatments and experience relapses, highlighting the need for ongoing research and development of new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. Abramson, HN.[2023]

In a phase 2 study involving 48 patients with relapsed/refractory multiple myeloma, the combination of pembrolizumab, pomalidomide, and dexamethasone resulted in a 60% objective response rate, with a median duration of response of 14.7 months.

The treatment showed acceptable safety, with 40% of patients experiencing grade 3 to 4 adverse events, but also indicated promising progression-free survival of 17.4 months, suggesting that this combination therapy can effectively enhance immune responses against multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Badros, A., Hyjek, E., Ma, N., et al.[2022]

In the GEM-Pembresid trial, pembrolizumab was tested as a consolidation treatment in multiple myeloma patients with persistent disease, but it only resulted in a decrease in M-protein in 1 out of 17 patients, indicating limited efficacy in this population.

While pembrolizumab had an acceptable safety profile, with some adverse events leading to treatment discontinuation, it did not enhance treatment responses, suggesting that it may not be beneficial as a consolidation therapy for patients with persistent measurable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. Puig, N., Corchete-Sánchez, LA., Pérez-Morán, JJ., et al.[2020]

The study presents results from a single-arm phase II trial involving elotuzumab, lenalidomide, and dexamethasone in patients with high-risk smoldering myeloma, indicating a focus on treatment efficacy.

The research investigates how the genetics of plasma cell clones and the immune microenvironment may serve as biomarkers to predict treatment response, highlighting the potential for personalized medicine in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are we ready to look beyond plasma cells in assessing high-risk smoldering myeloma? Maclachlan, KH., Lesokhin, AM.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. [2023]

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

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis. [2020]

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

Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. [2020]

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

Are we ready to look beyond plasma cells in assessing high-risk smoldering myeloma? [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]