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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how pembrolizumab, an immunotherapy drug, can help treat individuals with smoldering multiple myeloma, a slow-growing blood cancer at risk of spreading. Pembrolizumab boosts the immune system to better fight cancer cells. The study seeks participants diagnosed with intermediate or high-risk smoldering multiple myeloma, indicating a potential for more aggressive progression. As an Early Phase 1 trial, this research aims to understand how pembrolizumab works in people, offering participants the opportunity to be among the first to receive this treatment.

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.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab has been studied for its safety in treating multiple myeloma, including its early stages. In one study, 36% of patients experienced serious side effects requiring medical attention. However, another study found that pembrolizumab helped a high-risk patient with early-stage multiple myeloma achieve complete remission.

These findings suggest that while pembrolizumab can be effective, it also carries a risk of significant side effects. Potential trial participants should consider these risks and discuss them with healthcare professionals to make informed decisions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the power of immunotherapy to target smoldering multiple myeloma, a condition that often progresses to full-blown multiple myeloma. While standard treatments for multiple myeloma typically involve chemotherapy and targeted therapies, pembrolizumab uses an entirely different approach by unlocking the immune system's ability to recognize and attack cancer cells. This immune checkpoint inhibitor specifically blocks the PD-1 pathway, potentially preventing cancer cells from evading immune detection. Researchers are excited about pembrolizumab because it offers a novel mechanism of action that could provide significant benefits for patients at an earlier stage of this disease.

What evidence suggests that pembrolizumab might be an effective treatment for smoldering multiple myeloma?

Research has shown that pembrolizumab, the treatment under study in this trial, may effectively treat smoldering multiple myeloma, especially in high-risk patients. In one study, a patient with high-risk smoldering multiple myeloma achieved complete remission after receiving pembrolizumab. Another study found that pembrolizumab helped 62% of patients reach minimal residual disease (MRD) negativity, indicating only a few cancer cells remained. These findings are promising, suggesting pembrolizumab might enhance the immune system's ability to target and combat this type of cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Neeraj Saini, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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, 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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693011/

A pilot study of pembrolizumab in smoldering myeloma Pembrolizumab induced a complete remission in a patient with high-risk smoldering multiple myeloma who also had high-risk myeloma features.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02636010

Pembrolizumab (MK-3475) in MM Patients With Residual ... This is a national, multicenter, open label single-arm, non-comparative study that will determine the efficacy, safety and the changes in selected ...

3. trial.medpath.com trial.medpath.com/clinical-trial/ec3578618292d253/nct03221634-efficacy-safety-pembrolizumab-daratumumab-relapsed-refractory-multiple-myeloma

Efficacy and Safety Study of Pembrolizumab (MK-3475) in ... The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with daratumumab in participants with relapsed ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12466189/

Efficacy and toxicity of treatment of smoldering multiple ... Minimal residual disease (MRD) negativity rate was 62% (95% CI, 42%–81%), and grade 3–4 adverse events (AEs) rate was 36% (95% CI, 30%–43%). As ...

5. ashpublications.org ashpublications.org/blood/article/130/Supplement%201/3089/80717/Pilot-Study-of-Pembrolizumab-for-Immunoprevention

Pilot Study of Pembrolizumab for Immunoprevention in ... Here, we report the results of a pilot study evaluating the safety and efficacy of pembrolizumab in intermediate- and high-risk SMM patients (I- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02036502

NCT02036502 | A Study of Pembrolizumab (MK-3475) in ... This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and ...