This study is testing whether a lower dose of belantamab mafodotin used together with pomalidomide and dexamethasone can provide similar effectiveness with fewer side effects compared with the standard dose in patients with relapsed or refractory multiple myeloma. Participants will be randomly assigned to receive either a reduced dose or a standard dose of belantamab mafodotin in combination with pomalidomide and dexamethasone. The study will evaluate treatment response, side effects, and minimal residual disease (MRD), which is a measure of the number of myeloma cells that remain after treatment. The goal is to determine whether treatment can be optimized while maintaining disease control and reducing treatment-related toxicity.
Multiple myeloma remains an incurable plasma cell malignancy despite substantial advances in treatment. Although currently available therapies have improved patient outcomes, most patients eventually experience disease relapse and require additional treatment options. Therefore, there remains a need to optimize therapeutic strategies that can provide durable disease control while minimizing treatment-related toxicity. Belantamab mafodotin is a B-cell maturation antigen (BCMA)-targeted antibody-drug conjugate that has demonstrated clinically meaningful anti-myeloma activity in patients with relapsed or refractory multiple myeloma. Combination treatment with belantamab mafodotin, pomalidomide, and dexamethasone represents a promising therapeutic approach for this patient population. However, treatment-related adverse events, particularly ocular toxicities, may require dose modifications or treatment interruptions and can affect the overall treatment experience. The REBEL study has been designed to investigate whether a reduced-dose strategy of belantamab mafodotin can maintain clinical benefit while improving tolerability. The study will also evaluate the use of minimal residual disease (MRD) assessment as part of a treatment-guidance approach. MRD has emerged as an important measure of treatment response and may provide additional information about the depth and durability of disease control in multiple myeloma. By evaluating treatment effectiveness, safety, and MRD outcomes, this study aims to generate evidence that may support a more individualized approach to belantamab mafodotin-based therapy in patients with relapsed or refractory multiple myeloma. The results may help define treatment strategies that optimize the balance between disease control and treatment burden.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
228
Belantamab mafodotin is administered intravenously in combination with pomalidomide and dexamethasone. The study evaluates a reduced-dose strategy versus a standard-dose strategy of belantamab mafodotin in patients with relapsed or refractory multiple myeloma.
Pomalidomide is administered orally in combination with belantamab mafodotin and dexamethasone. Participants receive pomalidomide according to the protocol-defined treatment regimen
Dexamethasone is administered orally in combination with belantamab mafodotin and pomalidomide. Participants receive dexamethasone according to the protocol-defined treatment regimen
Overall Response Rate (ORR)
Overall Response Rate (ORR), defined as the proportion of participants achieving at least a partial response according to International Myeloma Working Group (IMWG) response criteria.
Time frame: From randomization up to approximately 6 years
Incidence of Grade 2 or Higher Ocular Toxicity
Incidence of ocular toxicity of at least Grade 2 severity, assessed using the keratopathy and visual acuity (KVA) scale and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Time frame: From randomization up to approximately 6 years
Incidence and Severity of Adverse Events
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), Grade 3 or higher adverse events, and Grade 3 or higher laboratory toxicities, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time frame: From first study treatment dose up to approximately 6 years
Undetectable Measurable Residual Disease (uMRD) Rate
Percentage of participants with measurable residual disease (MRD) less than 10\^-5 in bone marrow among participants in complete response at 6, 12, 18, 24, 30, 36, and 42 months from randomization.
Time frame: At 6, 12, 18, 24, 30, 36, and 42 months from randomization
Sustained Undetectable Measurable Residual Disease (uMRD) Negativity Rate
Percentage of participants with sustained undetectable measurable residual disease (uMRD) negativity, defined as two consecutive MRD-negative results in participants with complete response separated by at least 12 months.
Time frame: From randomization up to approximately 6 years
Overall Response Rate (ORR)
Percentage of participants achieving an overall response, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), according to International Myeloma Working Group (IMWG) criteria.
Time frame: From randomization up to approximately 6 years
Complete Response (CR) Rate
Percentage of participants achieving at least a complete response (CR) according to International Myeloma Working Group (IMWG) criteria.
Time frame: From randomization up to approximately 6 years
Very Good Partial Response (VGPR) Rate
Percentage of participants achieving at least a very good partial response (VGPR) according to International Myeloma Working Group (IMWG) criteria.
Time frame: From randomization up to approximately 6 years
Duration of Response (DoR)
Duration of response (DoR), defined as the time from first documented response to disease progression or death, whichever occurs first.
Time frame: From first documented response up to approximately 6 years
Progression-Free Survival (PFS)
Progression-free survival (PFS), defined as the time from randomization to disease progression or death from any cause, whichever occurs first.
Time frame: From randomization up to approximately 6 years
Overall Survival (OS)
Overall survival (OS), defined as the time from randomization to death from any cause.
Time frame: From randomization up to approximately 6 years
Duration of CR-MRD-Negative Disease (DoR-MRD)
Duration of CR-MRD-negative disease (DoR-MRD), defined as the time from achievement of complete response with MRD negativity to disease progression or death, whichever occurs first.
Time frame: From first documented CR-MRD-negative disease up to approximately 6 years
Change From Baseline in EORTC QLQ-C30 Score
Change from baseline in quality of life as assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Time frame: From randomization up to approximately 6 years
Change From Baseline in EORTC QLQ-MY20 Score
Change from baseline in quality of life as assessed using the European Organisation for Research and Treatment of Cancer Myeloma Module Quality of Life Questionnaire (EORTC QLQ-MY20).
Time frame: From randomization up to approximately 6 years
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