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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of stopping ongoing maintenance therapy in patients with multiple myeloma after an autologous stem cell transplant, where a patient's own stem cells replace damaged bone marrow. The main goal is to determine if patients who are MRD-negative can safely discontinue maintenance treatment without cancer progression. Eligible participants should have multiple myeloma, have been on maintenance therapy (such as Revlimid) for at least two years post-transplant, and show a very good or complete response to treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that stopping ongoing treatment in patients with multiple myeloma (a type of blood cancer) can be safe. In one study, all patients remained alive three years after stopping the treatment. Another study found that 85% of patients had no detectable cancer cells for a year after stopping therapy, suggesting the treatment was well-tolerated.

While stopping treatment can be safe, some patients who continue treatment beyond three years may experience longer periods without cancer recurrence. However, ongoing treatment can cause side effects such as tiredness, numbness, and stomach issues.

In summary, stopping treatment after a certain period has demonstrated positive results in terms of safety and tolerability, offering hope for a future without ongoing treatment for some patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of safely discontinuing maintenance therapy for multiple myeloma in patients who have achieved minimal residual disease (MRD)-negative status after at least three years of treatment. Unlike the current continuous maintenance approach, which often involves ongoing medication, this trial aims to determine if some patients can maintain their remission without the need for prolonged therapy. The potential to reduce or eliminate long-term medication not only minimizes side effects but also enhances the quality of life for patients.

What evidence suggests that discontinuing maintenance therapy could be effective for multiple myeloma?

Research has shown that stopping ongoing treatment for multiple myeloma patients with no detectable cancer cells (known as MRD-negative) can be effective. In one study, 75.8% of patients remained free of treatment and stable 36 months after stopping their maintenance therapy. Another study found that 85% of patients stayed MRD-negative, meaning no cancer cells were found, 12 months after stopping treatment. However, not all patients remain stable; some may see their disease return. In this trial, participants who are MRD-negative will discontinue maintenance therapy after at least three years, while those who are MRD-positive will continue maintenance therapy as per standard of care. Overall, these findings suggest that stopping maintenance therapy might be a safe option for those who are MRD-negative. ^{3 5 6 7 8}

Who Is on the Research Team?

Karen Sweiss, PhamD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11219377/

The impact of continuous lenalidomide maintenance treatment ... Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival.

2. ashpublications.org ashpublications.org/blood/article/145/20/2353/535778/Sustained-bone-marrow-and-imaging-MRD-negativity

Sustained bone marrow and imaging MRD negativity for 3 ... Key PointsThe TFS rate at 36 months after lenalidomide maintenance discontinuation was 75.8% (95% confidence interval, 64-90).

3. onclive.com onclive.com/view/mrd-negativity-is-sustained-after-cessation-of-lenalidomide-maintenance-in-multiple-myeloma

MRD Negativity Is Sustained After Cessation of ... Findings showed that among evaluable patients (n = 39), the MRD-negativity rate at 12 months following the end of maintenance therapy was 85% ( ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.106

Discontinuation of maintenance therapy in multiple ... Median follow-up was 30 months. Of 47 enrolled patients, 5 (11%) experienced disease progression and an additional 6 (13%) had MRD resurgence at ...

5. nature.com nature.com/articles/s41408-021-00548-7

The Effect of Duration of Lenalidomide Maintenance and ... Of the 126 patients who received salvage therapy, 80 (63%) patients relapsed while on maintenance or progressed within 60 days of stopping ...

6. ashpublications.org ashpublications.org/blood/article/145/20/2241/537123/Right-time-stopping-multiple-myeloma-maintenance

Right time: stopping multiple myeloma maintenance | Blood All patients were alive at a median follow-up of 3 years from the 3-year MRD− time point with a 7-year progression-free survival (PFS) from ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9573258/

Early versus Late Discontinuation of Maintenance Therapy ... We found that the patients receiving more than three years of maintenance therapy were more likely to have longer progression-free survival and overall survival ...

8. pharmacytimes.com pharmacytimes.com/view/discontinuing-lenalidomide-after-asct-may-be-safe-for-select-mrd-negative-patients-with-multiple-myeloma

Discontinuing Lenalidomide After ASCT May Be Safe for ... Discontinuing lenalidomide after 3 years of MRD negativity shows low relapse rates in multiple myeloma, offering hope for treatment-free ...