Belantamab Mafodotin for Multiple Myeloma

Overseen By Elisabet E. Manasanch

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Radiotherapy

Disqualifiers: Myeloma defining events, Hepatitis B/C, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safe dosage of Belantamab Mafodotin for individuals with high-risk smoldering multiple myeloma, a condition where abnormal plasma cells accumulate in the bone marrow. Participants will receive the treatment through an IV, which delivers medicine directly into a vein, to identify the optimal dose for future studies. It is suitable for those diagnosed with high-risk smoldering multiple myeloma who have not received standard chemotherapy for their condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, corticosteroids and radiotherapy are not allowed unless they are for specific conditions like stable chronic respiratory diseases. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Belantamab Mafodotin is likely to be safe for humans?

Research shows that belantamab mafodotin has been used in patients with relapsed or hard-to-treat multiple myeloma. Earlier studies identified eye-related side effects as the most common, with 48% of patients experiencing mild eye issues. Specifically, keratopathy, a condition affecting the cornea, was reported in 37.5% of patients.

These findings suggest that while belantamab mafodotin has potential, safety concerns exist, particularly regarding eye health. The FDA has approved this treatment for other uses, indicating a certain level of safety. However, as this is an early-stage trial, the complete safety profile for high-risk smoldering multiple myeloma remains under study. Participants should be aware of these possible side effects and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Belantamab mafodotin is unique because it targets a protein called BCMA, which is found on the surface of multiple myeloma cells. Unlike traditional treatments like proteasome inhibitors and immunomodulatory drugs, belantamab mafodotin is an antibody-drug conjugate. This means it combines an antibody that specifically seeks out cancer cells with a powerful anti-cancer agent that helps kill these cells. Researchers are excited about this treatment because it offers a new way to attack multiple myeloma, potentially improving outcomes for patients who have not responded to other treatments.

What evidence suggests that Belantamab Mafodotin might be an effective treatment for multiple myeloma?

Research has shown that Belantamab Mafodotin, which participants in this trial will receive, holds potential for treating multiple myeloma, a type of blood cancer. In earlier studies with patients whose cancer returned or didn't respond to treatment, Belantamab Mafodotin significantly reduced the risk of death and improved patient outcomes. Real-world evidence also supports its effectiveness, indicating it can be a valuable option for patients with limited treatment choices. While this trial focuses on high-risk smoldering multiple myeloma, positive results in other types suggest it might be beneficial here as well. ^{1 3 4 6 7}

Who Is on the Research Team?

Robert Orlowski

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk smoldering multiple myeloma who haven't had prior treatments. Participants need to have good kidney and liver function, be able to perform daily activities (ECOG 0-2), and agree to contraception. It's not for pregnant women, those with active hepatitis B/C or HIV, recent major surgery patients, or people with heart disease.

Inclusion Criteria

I have high-risk smoldering multiple myeloma with specific blood and bone marrow conditions.

My blood counts are within a healthy range.

My kidneys are working well enough (CrCl ≥ 30 ml/min).

Exclusion Criteria

I have been diagnosed with plasma cell leukemia.

I do not have active hepatitis B or C, HIV, or allergies to drugs similar to belantamab mafodotin.

My tests show signs of myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding

Determine the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD) of Belantamab Mafodotin

Up to 6 cycles of 56 days each

1 visit per cycle (in-person)

Dose-expansion

Treat additional patients at the MTD or RP2D to assess efficacy

Up to 6 cycles of 56 days each

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin

Trial Overview The study tests Belantamab Mafodotin's safety and optimal dose in two parts: finding the best dose among 18 patients then confirming it in another 12. The main goal is to see how well the drug works against this type of cancer by measuring response rates.

How Is the Trial Designed?

Group I: Belantamab mafodotin Experimental Treatment 1 Intervention

belantamab mafodotin by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.

Belantamab Mafodotin is already approved in European Union, United States for the following indications:

Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma

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) 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 106 heavily pretreated patients with relapsed/refractory multiple myeloma, belantamab mafodotin showed an overall response rate of 45.5% and a median overall survival of 14.5 months, indicating its efficacy in a real-world setting.

The treatment was associated with significant adverse effects, particularly ocular toxicity (68.4% experienced keratopathy), but the overall toxicity profile was considered tolerable, suggesting that the benefits may outweigh the risks for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study. Shragai, T., Magen, H., Lavi, N., et al.[2023]

In the DREAMM-2 study, after 13 months of follow-up, 32% of patients with relapsed or refractory multiple myeloma achieved an overall response to belantamab mafodotin (belamaf) at a dose of 2.5 mg/kg, indicating its efficacy in a heavily pretreated population.

The study found that belamaf maintained clinical activity without new safety concerns, even in patients experiencing prolonged dose delays due to corneal events, suggesting it is a safe treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Lonial, S., Lee, HC., Badros, A., et al.[2022]

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]

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) 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, an antibody-drug conjugate, has shown significant efficacy and manageable safety in treating heavily pretreated relapsed/refractory multiple myeloma, as demonstrated in the phase I DREAMM-1 and phase II DREAMM-2 studies.

The recommended dose of belantamab mafodotin is 2.5 mg/kg every 3 weeks, with safety outcomes like corneal events and thrombocytopenia being closely linked to drug exposure, highlighting the importance of monitoring patient characteristics and disease burden in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma. Ferron-Brady, G., Rathi, C., Collins, J., et al.[2022]

The budget impact analysis of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma indicates that its introduction would be budget neutral for a US health plan, with minimal cost changes over 3 years.

In a hypothetical health plan with 1 million members, only 33 patients were identified as eligible for treatment, and the analysis showed that the budget impact was most sensitive to treatment duration and drug acquisition costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. Shah, A., Tosh, JC., Ambavane, A., et al.[2022]

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]

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 ...