Maintenance Therapy Discontinuation for Multiple Myeloma

(HEME-20 Trial)

Overseen By Karen Sweiss, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Illinois at Chicago

Must be taking: Anti-myeloma therapy

Disqualifiers: Plasma cell leukemia, AL amyloidosis, POEMS, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

50 Participants Needed

Trial Summary

What is the purpose of this trial?

A pilot study to assess the risk of progression after stopping post-autologous stem cell transplant (ASCT) maintenance therapy in Minimal Residual Disease (MRD)-negative MM patients.

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 focuses on stopping maintenance therapy for multiple myeloma after a stem cell transplant. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of discontinuing maintenance therapy with Revlimid for multiple myeloma?

Research shows that maintenance therapy, including drugs like Revlimid, can improve disease control and survival in multiple myeloma patients. However, some studies suggest that for certain patients, stopping maintenance therapy might not significantly impact their survival, especially if they have achieved a good response to initial treatments. ^{1 2 3 4 5}

Is it safe to discontinue maintenance therapy with lenalidomide (Revlimid) for multiple myeloma?

Lenalidomide (Revlimid) is generally safe for use as maintenance therapy in multiple myeloma, but it can increase the risk of certain side effects like blood-related issues and a second primary cancer. However, the benefits in survival often outweigh these risks. ^{5 6 7 8 9}

How does the drug Revlimid differ from other treatments for multiple myeloma?

Revlimid (lenalidomide) is unique as it is the only drug approved for maintenance therapy in multiple myeloma, helping to delay disease progression and improve survival after initial treatment. It is preferred in guidelines due to its demonstrated safety and efficacy, unlike other treatments that have not shown clear benefits in maintenance settings. ^{2 7 10 11 12}

Research Team

Karen Sweiss, PhamD

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

This trial is for Multiple Myeloma patients who are MRD-negative after a stem cell transplant and have been on maintenance therapy for at least 2 years. They should be in good physical condition (ECOG ≤2) and have had a very good partial response or complete remission. It's not open to those with certain other plasma disorders, prior organ transplants, or those on immunosuppressive therapy.

Inclusion Criteria

I have been active and mostly self-sufficient in the last month.

My multiple myeloma is classified as stage I, II, or III.

I have been diagnosed with multiple myeloma according to IMWG criteria.

Exclusion Criteria

I am unable to sign the consent form myself.

Treatment with any investigational drug within 30 days prior to enrollment

I have had an organ transplant or need medicine to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRD Testing

MRD testing performed on routine bone marrow aspirate using next-generation sequencing

1-2 weeks

1 visit (in-person)

Maintenance Discontinuation

MRD-negative patients discontinue maintenance therapy after at least three years

3 years

Follow-up

Participants are monitored for progression and MRD status using IMWG criteria

3 years

Yearly visits (in-person)

Treatment Details

Interventions

• Discontinue maintenance therapy SOC

Trial Overview The FREEDMM Trial is testing the safety of stopping standard maintenance drugs used after an autologous stem cell transplant in patients with no minimal residual disease. The goal is to see if halting treatment affects the risk of their cancer progressing.

Participant Groups

Group I: Bone marrow MRD-positive VGPR or CR Experimental Treatment 1 Intervention

Continue maintenance therapy as per SOC

Group II: Bone marrow MRD-negative VGPR or CR Experimental Treatment 1 Intervention

Discontinue maintenance therapy after at least three years

Discontinue maintenance therapy SOC is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in Canada as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma

Approved in Japan as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes

Approved in China as Revlimid for:

• Multiple myeloma

Approved in Switzerland as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

The introduction of bortezomib and immunomodulatory drugs like thalidomide and lenalidomide has significantly improved response rates and survival in multiple myeloma patients, emphasizing the importance of achieving maximal response while considering patient quality of life.

Maintenance therapy is now recognized as a standard care practice, particularly for high-risk patients, as it enhances disease control and may improve overall survival, while multidrug regimens combining proteasome inhibitors and IMiDs are becoming the norm due to their strong response outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of response endpoints with survival outcomes in multiple myeloma. Lonial, S., Anderson, KC.[2022]

Maintenance therapy significantly improves progression-free survival (PFS) in transplant-ineligible multiple myeloma patients, with a hazard ratio of 0.48 based on a meta-analysis of five randomized controlled trials involving 1139 patients.

Despite the benefits in PFS, maintenance therapy does not improve overall survival and is associated with a higher risk of adverse events, highlighting the need to balance treatment benefits against potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis. Balitsky, AK., Karkar, A., McCurdy, A., et al.[2021]

Continuous maintenance therapy after initial treatment for multiple myeloma has been shown to significantly improve overall survival rates, with over 80% of patients surviving beyond 5 years when combined with high-dose melphalan and stem cell transplantation.

The use of minimal residual disease (MRD) status is being explored to tailor maintenance therapy, potentially allowing for the identification of patients who can safely limit treatment duration without compromising their survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future perspectives of maintenance therapy in multiple myeloma. Nagarajan, C., Tan, MS., Chen, Y., et al.[2021]

The introduction of new agents for treating multiple myeloma has improved patient outcomes, with continuous therapy showing better progression-free and overall survival rates, especially in younger patients after autologous transplantation.

Continuous treatment, including maintenance therapy, has been found to deepen treatment responses and control the disease more effectively over time, even in transplant-ineligible patients, compared to fixed-duration therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving Toward Continuous Therapy in Multiple Myeloma. Bonello, F., Cetani, G., Bertamini, L., et al.[2021]

Long-term continuous therapy and maintenance treatment approaches in multiple myeloma (MM) have shown to provide better disease control and improved patient outcomes compared to traditional fixed-duration treatments, potentially transforming MM into a chronic or functionally curable condition.

The review highlights the importance of using tolerable treatments that do not cause chronic toxicity or negatively impact quality of life, with various agents like lenalidomide and bortezomib being investigated for their effectiveness in newly diagnosed MM across different treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma. Dimopoulos, MA., Jakubowiak, AJ., McCarthy, PL., et al.[2023]

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]

Thalidomide was the first maintenance therapy to show a clear benefit in progression-free survival (PFS) for multiple myeloma patients after high-dose therapy, marking a significant advancement in treatment options.

Emerging therapies like lenalidomide and bortezomib are being investigated for their potential to reduce relapse risk, but further research is needed to determine optimal dosing, duration, and long-term effects on survival and disease aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy for myeloma: how much, how long, and at what cost? Attal, M., Roussel, M.[2020]

Lenalidomide significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation, as shown in randomized trials like the FIRST and MM-015 trials.

Continuous lenalidomide therapy is associated with less toxicity compared to thalidomide, maintaining tolerability without increasing the risk of neutropenia or second primary malignancies, making it a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. McCormack, PL.[2018]

The median survival for multiple myeloma patients has significantly improved to nearly 50% at 10 years, thanks to advancements in combination induction therapy, autologous stem-cell transplant, and lenalidomide maintenance.

Current maintenance therapies aim to minimize treatment-related toxicities while extending survival or progression-free survival, highlighting the need for research into therapy cessation and tailored treatment approaches to avoid overtreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy and need for cessation studies in multiple myeloma: Focus on the future. Diamond, B., Maclachlan, K., Chung, DJ., et al.[2020]

Maintenance therapy in multiple myeloma, particularly with lenalidomide, has been shown to effectively delay disease progression and improve both progression-free and overall survival, based on clinical trial data.

While lenalidomide is the preferred agent for maintenance therapy and has demonstrated safety and efficacy, ongoing research is exploring the use of newer agents in combination with established treatments to enhance outcomes in relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance and continuous therapy for multiple myeloma. Richardson, PG., Laubach, J., Gandolfi, S., et al.[2019]

Recent studies suggest that thalidomide-based maintenance therapy can significantly prolong overall survival in multiple myeloma patients after autologous stem cell transplantation, marking a potential breakthrough in maintenance treatment.

Ongoing trials are investigating the effectiveness of lenalidomide and bortezomib as maintenance therapies, aiming to clarify their roles and optimize treatment strategies for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of maintenance therapy in the treatment of multiple myeloma. Badros, AZ.[2019]

Maintenance therapies for multiple myeloma have been shown to improve survival rates following initial treatment, emphasizing their importance in patient care.

Current clinical trials are exploring various maintenance strategies, but there is concern that high-risk myeloma patients may not be receiving therapies aligned with established US guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Landscape of Currently Enrolling Maintenance Trials in Multiple Myeloma. Tariq, SM., Abdallah, AO., Goodman, A., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Association of response endpoints with survival outcomes in multiple myeloma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Current and future perspectives of maintenance therapy in multiple myeloma. [2021]

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

Moving Toward Continuous Therapy in Multiple Myeloma. [2021]

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

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma. [2023]

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

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

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

Maintenance therapy for myeloma: how much, how long, and at what cost? [2020]

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

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Maintenance therapy and need for cessation studies in multiple myeloma: Focus on the future. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Maintenance and continuous therapy for multiple myeloma. [2019]

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

The role of maintenance therapy in the treatment of multiple myeloma. [2019]

12. England pubmed.ncbi.nlm.nih.gov

The Landscape of Currently Enrolling Maintenance Trials in Multiple Myeloma. [2023]