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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two treatments, belantamab mafodotin (an antibody-drug conjugate) and lenalidomide (an immunomodulatory drug), can improve disease status in patients with multiple myeloma, a type of blood cancer, after a stem cell transplant. Specifically, the researchers seek to find out if this combination can convert minimal residual disease-positive patients (those with a small number of cancer cells remaining after treatment) to negative, indicating a deeper response to therapy. Individuals recently diagnosed with multiple myeloma who have undergone a stem cell transplant might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that belantamab mafodotin can cause some side effects. One study found that about 48% of patients experienced eye-related side effects, most of which were mild. Keratopathy appeared in 37.5% of patients. For most, these side effects were not severe.

Studies indicate that lenalidomide is generally well-tolerated. In a large study, 23% of patients reported a decreased appetite. However, only 3% experienced weight loss or malnutrition, suggesting that serious issues are rare.

Overall, both treatments have some side effects, but they are mostly manageable. This information may be helpful for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Belantamab Mafodotin and Lenalidomide for treating multiple myeloma because they offer unique approaches compared to standard options like proteasome inhibitors and immunomodulatory drugs. Belantamab Mafodotin is an antibody-drug conjugate that targets the BCMA protein on myeloma cells, delivering a powerful drug directly to the cancer cells, minimizing harm to healthy cells. Lenalidomide, taken orally, modulates the immune system to fight cancer cells and is known for its manageable side effect profile. Together, these treatments could offer a more targeted and potentially effective approach with fewer side effects.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that belantamab mafodotin, one of the treatments in this trial, may lower the risk of death for patients with relapsed or hard-to-treat multiple myeloma. One study found it reduced the risk of death by 51%, a significant finding. Real-world studies also highlight its effectiveness, especially for patients with limited treatment options.

Lenalidomide, another treatment option in this trial, is a well-researched therapy for multiple myeloma. A study demonstrated that it significantly increased the overall survival of patients. However, results can vary, and some patients might require additional treatments for better outcomes. This trial will evaluate the effectiveness of using belantamab mafodotin and lenalidomide separately, which could enhance the overall effectiveness of treatment for newly diagnosed multiple myeloma. ^{1 3 4 6 7}

Who Is on the Research Team?

Qaiser Bashir

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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]

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 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) 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]

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]

Citations

1. gsk.com gsk.com/en-gb/media/press-releases/blenrep-approved-by-us-fda-for-use-in-treatment-of-relapsedrefractory-multiple-myeloma/

Blenrep approved by US FDA for use in treatment of ... Significant unmet need for patients requires new and novel treatments1; DREAMM-7 showed a 51% reduction in the risk of death and tripled ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40348718/

Treatment Patterns, Efficacy, and Tolerability of ... Treatment Patterns, Efficacy, and Tolerability of Belantamab Mafodotin in Patients With Relapsed and/or Refractory Multiple Myeloma: A Real-World Analysis.

3. nature.com nature.com/articles/s41408-025-01226-8

A real-world experience of efficacy and safety ... We report the real-world safety and efficacy outcomes of standard-of-care belantamab mafodotin for RRMM, with the aim to determine the patterns of its use in a ...

4. haematologica.org haematologica.org/article/view/haematol.2022.281772

Real-world study of the efficacy and safety of belantamab ... “Real-life” data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma- the Mayo Clinic experience. Blood. 2021 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04246047

Study Details | NCT04246047 | Evaluation of Efficacy and ... This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone ( ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37078253/

Real-world study of the efficacy and safety of belantamab ... Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2403407

Belantamab Mafodotin, Pomalidomide, and ... Data from a phase 1–2 trial involving patients with relapsed or refractory myeloma showed some safety concerns but promising clinical activity of belantamab ...