Individualized Treatment Plans for Multiple Myeloma

Overseen By Andrew Cowan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Antibiotics, Immunosuppressants, Prednisone

Disqualifiers: Bleeding, Infection, Other malignancy, others

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

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies whether using high throughput drug sensitivity and genomics data is feasible in developing individualized treatment in patients with multiple myeloma or plasma cell leukemia that has come back or does not respond to treatment. High throughput screen tests many different drugs that kill multiple myeloma cells in individual chambers at the same time. Matching a drug or drug combination to a patient using high throughput screen and genetic information may improve the ability to help patients by choosing drugs that work well for their disease.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had previous treatments for multiple myeloma within 2 weeks of starting the study treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that previous treatments for multiple myeloma should not have been given within 2 weeks before starting the study treatment.

What data supports the idea that Individualized Treatment Plans for Multiple Myeloma is an effective treatment?

The available research shows that Individualized Treatment Plans for Multiple Myeloma, like the Ex vivo Mathematical Myeloma Advisor (EMMA), can accurately predict how patients will respond to different drugs. In a study with 52 patients, EMMA correctly identified 96% of responders and non-responders. Another study used a 7-gene signature to predict which patients would benefit most from specific drug combinations, leading to better survival outcomes. These personalized approaches help choose the most effective treatments, improving patient outcomes compared to standard treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment High Throughput Screening for Multiple Myeloma?

High Throughput Screening (HTS) has shown promise in predicting treatment responses for multiple myeloma by testing a wide range of drugs on patient samples to identify the most effective options. Studies have demonstrated that HTS can guide personalized treatment plans by revealing drug sensitivities and genetic profiles, potentially improving outcomes for patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

What safety data exists for individualized treatment plans for multiple myeloma?

The safety data for individualized treatment plans for multiple myeloma includes information from various studies and reports. The FDA's boxed warnings impact adverse drug reactions reporting rates for multiple myeloma drugs, highlighting the importance of monitoring these reactions. Novel agents have specific side effect profiles, and guidelines exist for managing these adverse events. Post-marketing safety data from the FDA's Adverse Event Reporting System shows that immunomodulatory drugs (IMiDs) like thalidomide, lenalidomide, and pomalidomide have significant adverse event signals, including cardiac, gastrointestinal, and respiratory disorders. Real-world data indicates that treatment decisions should consider efficacy, safety, tolerability, and quality of life, as many patients do not meet clinical trial criteria. Patient-reported outcomes and physician-patient concordance on side effects are also important for understanding treatment impact. ^{6 7 8 9 10}

What safety data exists for individualized treatment plans for multiple myeloma?

Safety data for multiple myeloma treatments show that new drugs can have specific side effects, such as heart issues with thalidomide, stomach problems with lenalidomide, and breathing issues with pomalidomide. These treatments have been linked to serious conditions like pneumonia and kidney failure, but further research is needed to confirm these findings. ^{6 7 8 9 10}

Is High Throughput Screening a promising treatment for multiple myeloma?

Yes, High Throughput Screening is a promising treatment for multiple myeloma because it helps doctors predict how well a patient will respond to different drugs, allowing for personalized treatment plans. This approach can lead to better treatment outcomes by identifying the most effective drugs for each individual patient. ^{1 3 5 11 12}

How does the treatment High Throughput Screening differ from other treatments for multiple myeloma?

High Throughput Screening (HTS) for multiple myeloma is unique because it uses a large-scale testing method to predict how a patient's cancer cells will respond to different drugs, allowing for a personalized treatment plan. This approach integrates genetic and molecular data to tailor therapy, unlike traditional treatments that may not consider individual patient differences. ^{1 3 5 11 12}

Research Team

Andrew Cowan, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with relapsed or refractory multiple myeloma or plasma cell leukemia who have tried at least three prior treatments, including an IMiD and a PI. They must be able to consent, practice birth control if applicable, have adequate organ function, and measurable disease. Excluded are those with HIV/hepatitis B/C, recent major treatments like SCT within 12 weeks, active infections requiring antibiotics within 7 days of study start.

Inclusion Criteria

Your blood test shows high levels of a specific protein called free light chain and an abnormal ratio of certain proteins in your blood.

A sample from my bone marrow or tissue with enough cells for testing has been collected.

You have a disease that can be measured by specific criteria.

Exclusion Criteria

I have another cancer that is expected to affect my life for less than a year.

Pregnant or breast feeding women

Any medical conditions that would impose excessive risk to the patient, or would adversely affect his/her participation in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High-throughput Assay and Sequencing

Patients undergo collection of bone marrow aspirate and blood for high-throughput drug sensitivity assay and mutational analysis using next generation sequencing.

Up to 3 weeks

1 visit (in-person)

Treatment Decision

Patients and their treating physicians receive the results of the tests and make treatment decisions.

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 2 years

Treatment Details

Interventions

• High Throughput Screening

Trial Overview The trial tests the feasibility of using high throughput drug sensitivity screening alongside genomics data to personalize treatment for patients whose multiple myeloma or plasma cell leukemia has returned after treatment or is resistant. It involves collecting samples from patients and testing many drugs simultaneously to find effective ones based on genetic information.

Participant Groups

Group I: Device feasibility (high-throughput assay, sequencing) Experimental Treatment 3 Interventions

Patients undergo collection of bone marrow aspirate and blood for high-throughput drug sensitivity assay and mutational analysis using next generation sequencing. Patients and their treating physicians receive the results of the tests. Treatment decisions are then made by the patients and their treating physicians.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Findings from Research

The Ex vivo Mathematical Myeloma Advisor (EMMA) system can predict patient-specific responses to multiple myeloma treatments within 5 days of a bone marrow biopsy, achieving a 96% accuracy in classifying patients as responders or nonresponders.

In a study of 52 patients, EMMA identified that 60% were treated with ineffective therapies, suggesting that the platform could help optimize treatment choices and improve patient outcomes by recommending more effective drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma. Silva, A., Silva, MC., Sudalagunta, P., et al.[2021]

A 7-gene signature developed from RNA sequencing of newly diagnosed multiple myeloma patients can predict which treatment regimens (bortezomib or lenalidomide) will be more effective for individual patients, enhancing personalized therapy.

Patients treated according to this gene signature showed significantly better progression-free survival (20.1 months vs not reached) and overall survival (30.7 months vs not reached) compared to those who were not, indicating that this approach could optimize treatment outcomes in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature. Chapman, MA., Sive, J., Ambrose, J., et al.[2023]

This study analyzed drug and immunotherapy sensitivities in 101 bone marrow samples from 70 multiple myeloma patients, revealing that specific genetic and molecular factors, such as DNA repair pathways and EYA3 expression, influence how patients respond to treatments like proteasome inhibitors and elotuzumab.

The findings indicate that understanding the bone marrow microenvironment and individual patient characteristics can help tailor personalized treatment strategies, potentially improving clinical outcomes for multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. Kropivsek, K., Kachel, P., Goetze, S., et al.[2023]

In a study of 76 FDA-approved oncology drugs tested on 25 multiple myeloma and 15 non-Hodgkin's lymphoma cell lines, proteasome inhibitors and other agents showed the broadest effectiveness against primary multiple myeloma samples, indicating their potential as key treatments.

The research identified specific genomic biomarkers linked to drug sensitivity, such as increased responsiveness to venetoclax in patients with the t(11;14) mutation, suggesting that personalized treatment strategies could be developed based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Direct to Drug" screening as a precision medicine tool in multiple myeloma. Bonolo de Campos, C., Meurice, N., Petit, JL., et al.[2021]

A clinical trial involving 25 patients with relapsed or refractory multiple myeloma successfully used high-throughput screening (HTS) of 170 compounds to predict treatment responses, with actionable results available within 5 days.

Among the 13 patients who received therapy guided by the HTS results, 92% achieved stable disease or better, highlighting the potential of personalized treatment strategies based on drug sensitivity testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma. Coffey, DG., Cowan, AJ., DeGraaff, B., et al.[2023]

The study analyzed the impact of FDA-issued boxed warnings on the reporting rates of adverse drug reactions (ADRs) for multiple myeloma drugs, finding that awareness of ADRs increased significantly after warnings were issued.

Out of 10 drug/ADR combinations studied, six showed a rise in reporting rates for serious adverse events post-warning, suggesting that boxed warnings effectively enhance pharmacovigilance and awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of United States Food and Drug Administration's boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs. Garg, V., Raisch, DW., McKoy, JM., et al.[2021]

Recent advancements in multiple myeloma treatment have introduced several new drugs that significantly improve patient outcomes, each with unique mechanisms of action and side effect profiles.

The review emphasizes the importance of monitoring and managing specific adverse events associated with these new treatments, providing practical guidance for healthcare providers to enhance patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Ludwig, H., Delforge, M., Facon, T., et al.[2023]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

Approximately 40% of multiple myeloma patients do not meet the criteria for phase 3 clinical trials, highlighting the need for treatment decisions that consider real-world factors like patient adherence, treatment feasibility, and quality of life.

Individual patient perspectives on treatment efficacy vary widely, necessitating a personalized approach to therapy that incorporates each patient's unique goals and experiences throughout their treatment journey.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life. Terpos, E., Mikhael, J., Hajek, R., et al.[2021]

In a study involving 132 multiple myeloma patients and 63 physicians, it was found that patients who reported higher levels of bother from side effects experienced significantly lower health-related quality of life (HRQoL) scores, indicating a direct impact of side effects on patient well-being.

There was a notable lack of agreement between patients and physicians regarding the perception of side effects, highlighting the need for better communication in managing treatment and side effects in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world patient-reported outcomes and concordance between patient and physician reporting of side effects across lines of therapy in multiple myeloma within the USA. Ribbands, A., Boytsov, N., Bailey, A., et al.[2023]

The mass accumulation rate (MAR) assay effectively measures the drug sensitivity of multiple myeloma cells, providing a rapid and accurate way to assess how these cells respond to various standard treatments.

In clinical applications, the MAR assay successfully predicted the therapeutic responses of nine patients based on their diagnoses, suggesting it could be a valuable tool for personalizing treatment strategies in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. Cetin, AE., Stevens, MM., Calistri, NL., et al.[2019]

The study developed an advanced preclinical platform using microfluidic technology and patient-derived tumor samples to better predict the effectiveness of cancer drugs, specifically for multiple myeloma, an incurable bone marrow cancer.

This platform successfully predicted the sensitivity of multiple myeloma cells to established treatments like bortezomib and melphalan, and it can also explore drug resistance and combinations, enhancing personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preclinical assay for chemosensitivity in multiple myeloma. Khin, ZP., Ribeiro, ML., Jacobson, T., et al.[2021]

References

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

An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma. [2021]

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

RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature. [2023]

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

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. [2023]

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

"Direct to Drug" screening as a precision medicine tool in multiple myeloma. [2021]

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

High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Impact of United States Food and Drug Administration's boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]

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

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life. [2021]

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

Real-world patient-reported outcomes and concordance between patient and physician reporting of side effects across lines of therapy in multiple myeloma within the USA. [2023]

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

Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. [2019]

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

A preclinical assay for chemosensitivity in multiple myeloma. [2021]