Belantamab Mafodotin + Lenalidomide for Multiple Myeloma

Overseen By Qaiser Bashir

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Lenalidomide

Must not be taking: Systemic steroids

Disqualifiers: Progressive disease, Plasma cell leukemia, Unstable liver, Active renal condition, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

94 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have used an investigational drug or certain anti-myeloma therapies within 14 days before starting the study, and you must not have received a monoclonal antibody treatment within 30 days before the study.

What data supports the effectiveness of the drug combination Belantamab Mafodotin and Lenalidomide for treating multiple myeloma?

The research shows that lenalidomide, when combined with other drugs like dexamethasone, has been effective in treating multiple myeloma, especially in elderly patients. This suggests that lenalidomide could be a beneficial component in combination therapies for multiple myeloma. ^{1 2 3 4 5}

Is Belantamab Mafodotin + Lenalidomide safe for humans?

Belantamab Mafodotin has been associated with eye-related side effects, such as changes in vision and dry eyes, which are common and sometimes severe. It is only available through a special program due to these risks. Other side effects include low blood platelet levels and infections, but the safety profile is considered manageable with proper monitoring. ^{6 7 8 9 10}

How is the drug Belantamab Mafodotin + Lenalidomide unique for treating multiple myeloma?

Belantamab Mafodotin is a first-in-class antibody-drug conjugate that targets B-cell maturation antigen (BCMA) on myeloma cells, delivering a powerful cancer-killing agent directly to the tumor. This approach is unique because it combines targeted therapy with a cytotoxic payload, offering a novel mechanism of action compared to traditional treatments for multiple myeloma. ^{8 10 11 12 13}

What is the purpose of this trial?

To increase the conversion rate from MRD-positive to MRD-negative CR in patients with newly diagnosed multiple myeloma (NDMM) receiving post-transplant maintenance therapy with belantamab mafodotin plus lenalidomide.

Research Team

Qaiser Bashir

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults aged 18-75 with newly diagnosed multiple myeloma who have had a stem cell transplant. They must be partially responsive to treatment, in good physical condition, and able to follow strict birth control guidelines. People with progressive disease, certain other myeloma types, eye diseases, recent major surgery or known allergies to the drugs can't join.

Inclusion Criteria

I cannot become pregnant due to my age or medical reasons.

I agree to use contraception or practice abstinence.

My organs are working well.

Exclusion Criteria

I have an active kidney condition.

You have tested positive for hepatitis C unless you meet specific criteria.

I have not had major surgery in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin by vein on Day 1 and lenalidomide by mouth every day of each cycle for maintenance therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Belantamab Mafodotin
• Lenalidomide

Trial Overview The study tests if adding Belantamab Mafodotin to Lenalidomide after a stem cell transplant helps patients achieve better outcomes by turning more MRD-positive cases into MRD-negative ones.

Participant Groups

Group I: Lenalidomide Experimental Treatment 1 Intervention

lenalidomide by mouth every day of each cycle

Group II: Belantamab mafodotin Experimental Treatment 1 Intervention

belantamab mafodotin by vein over about 30 minutes on Day 1 of each cycle

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 1162 multiple myeloma patients, those treated with the combination of thalidomide, melphalan, and prednisone (MPT) showed significantly better overall survival (OS) rates compared to those treated with melphalan and prednisone (MP) alone, with median OS of 4.2 years for MPT versus 2.2 years for MP in the first line of treatment.

The relative risk of death was reduced by 39% in the MPT group compared to the MP group in the first line of therapy, indicating that MPT is a more effective treatment option for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma--a retrospective population based study of 1162 patients. Lund, J., Uttervall, K., Liwing, J., et al.[2013]

Mycophenolate mofetil (MMF) is commonly used to treat Membranous Glomerulonephropathy (MGN), but this case report highlights a rare side effect: acquired sensory-motor axonal polyneuropathy in a 66-year-old male patient.

This case is significant as it documents a previously unreported adverse effect of MMF, emphasizing the need for awareness of potential neurological complications in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil-induced peripheral neuropathy in the treatment of membranous glomerulonephropathy: A case report. Moghimi, M., Nekoukar, Z., Gholami, F.[2021]

In a study comparing lenalidomide-dexamethasone (len/dex) and melphalan-prednisone-lenalidomide (MPR) in 89 elderly patients with myeloma, both treatments showed similar efficacy in terms of time to progression, progression-free survival, and overall survival, indicating that either regimen can be effective for this patient group.

However, MPR was associated with significantly higher rates of severe hematologic toxicities, such as neutropenia and thrombocytopenia, suggesting that while both treatments are effective, len/dex may be a safer option with fewer severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. Gay, F., Vincent Rajkumar, S., Falco, P., et al.[2018]

In a study of 40 patients with membranous nephropathy, the addition of mycophenolate mofetil (MMF) to tacrolimus (TAC) did not significantly reduce the relapse rate of nephrotic syndrome after treatment cessation, with relapse rates of 50% for TAC alone and 42% for TAC plus MMF.

Both treatment groups achieved similar remission rates (80% for TAC vs. 95% for TAC/MMF) and median times to remission (54 weeks for TAC vs. 40 weeks for TAC/MMF), indicating that while MMF did not improve outcomes, it also did not negatively impact safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. Nikolopoulou, A., Condon, M., Turner-Stokes, T., et al.[2020]

In a 24-week study involving 75 rheumatoid arthritis patients, tacrolimus (TAC) combined with methotrexate (MTX) was found to be non-inferior in efficacy compared to leflunomide (LEF) combined with MTX, indicating that TAC is an effective alternative treatment.

The safety profile of TAC was better than LEF, with fewer adverse events reported (49 in TAC group vs. 66 in LEF group), and lower instances of liver enzyme elevation (transaminitis) in the TAC group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of add-on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate. Shin, K., Baek, HJ., Kang, YM., et al.[2020]

Belantamab mafodotin (belamaf) is the first approved therapy targeting B-cell maturation antigen (BCMA) for treating relapsed and/or refractory multiple myeloma (RRMM), specifically for patients who have undergone at least four prior therapies, addressing a significant unmet need in this patient population.

While belamaf offers a new treatment option with outpatient administration, it is associated with frequent corneal ocular adverse events, necessitating a multidisciplinary approach for patient management involving both oncologists and eye care specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. Becnel, MR., Lee, HC.[2021]

Belantamab mafodotin (BLENREP) received accelerated FDA approval for treating relapsed or refractory multiple myeloma in adults who have undergone at least four prior therapies, showing an overall response rate of 31% to 34% in the DREAMM-2 trial with 2.5 or 3.4 mg/kg doses.

The most common side effect was keratopathy, affecting 71% to 77% of patients, leading to a boxed warning for ocular toxicity, indicating the need for careful monitoring and a restricted distribution program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Baines, AC., Ershler, R., Kanapuru, B., et al.[2023]

Belantamab mafodotin (belamaf) significantly improves overall survival (OS) and duration of response (DoR) in patients with relapsed/refractory multiple myeloma compared to selinexor plus low-dose dexamethasone, with a hazard ratio of 0.53 for OS and 0.41 for DoR, indicating its efficacy as a treatment option.

Belamaf also shows a favorable safety profile, with fewer severe adverse events compared to selinexor plus dexamethasone, making it a promising single-agent therapy for patients who have already undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. Prawitz, T., Popat, R., Suvannasankha, A., et al.[2022]

In a study of 156 patients with relapsed and refractory multiple myeloma, belantamab-mafodotin (belamaf) demonstrated an overall response rate of 41.8%, with significant improvements in progression-free survival for those achieving at least minimal response (MR).

The safety profile of belamaf was manageable, with corneal events being the most common adverse effects, affecting 87.9% of patients, though only 1.3% discontinued treatment due to ocular toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. de la Rubia, J., Alonso, R., Clavero, ME., et al.[2023]

Belantamab mafodotin (BLENREP™) is a promising new treatment for relapsed/refractory multiple myeloma, showing at least a partial response in heavily pre-treated patients, indicating its potential efficacy in difficult cases.

The treatment was well tolerated by the patients, suggesting a favorable safety profile, which is important for those who have already undergone multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. Condorelli, A., Garibaldi, B., Gagliano, C., et al.[2021]

Belantamab mafodotin (belamaf) is an approved treatment for adults with relapsed/refractory multiple myeloma, showing effectiveness by targeting BCMA and eliminating myeloma cells through multiple mechanisms.

The ongoing DREAMM-5 study is exploring the safety and efficacy of belamaf in combination with other novel therapies, which may enhance its anticancer effects compared to belamaf alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. Nooka, AK., Weisel, K., van de Donk, NW., et al.[2021]

Belantamab mafodotin (belamaf) is an effective treatment for relapsed or refractory multiple myeloma, showing a 32% overall response rate in the phase II DREAMM-2 study with 95 patients.

While most patients experienced microcyst-like epithelial changes (MECs) as a side effect, these were generally manageable, with a high resolution rate and no permanent vision loss reported, indicating a need for careful monitoring and collaboration between eye care and oncology professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq, AV., Degli Esposti, S., Popat, R., et al.[2020]

Belantamab mafodotin is a first-in-class monoclonal antibody-drug conjugate designed to treat relapsed or refractory multiple myeloma by targeting B-cell maturation antigen (BCMA) and delivering a cytotoxic agent directly to cancer cells.

It received regulatory approval in the USA and EU in August 2020 based on promising results from the DREAMM-2 trial, specifically for patients who have undergone at least four prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin: First Approval. Markham, A.[2021]

References

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

Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma--a retrospective population based study of 1162 patients. [2013]

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

Mycophenolate mofetil-induced peripheral neuropathy in the treatment of membranous glomerulonephropathy: A case report. [2021]

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

Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. [2018]

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

Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of add-on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate. [2020]

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

The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. [2021]

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

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. [2023]

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

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. [2021]

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

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]

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

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. [2020]

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

Belantamab Mafodotin: First Approval. [2021]