Phase II MRD‑guided Trial of Reduced vs Standard Dose Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Primary objective 1: demonstrate non‑inferiority of the reduced‑dose belantamab mafodotin regimen versus the standard dose with respect to overall response rate in patients with relapsed/refractory multiple myeloma. Primary objective 2: demonstrate that the reduced‑dose regimen lowers the incidence of ≥grade 2 ocular complications by at least 22 % compared with the standard regimen. Secondary objectives include: evaluation of safety and tolerability by incidence and severity of any adverse events, including Grade ≥3 events and laboratory toxicities; estimation of the rate of minimal residual disease negativity (uMRD <10⁻⁵) in bone marrow of patients achieving complete response at scheduled time points up to 42 months; determination of sustained uMRD negativity defined by two consecutive negative results ≥12 months apart; assessment of response rates (overall response rate, complete response, very good partial response, partial response) at designated disease‑assessment visits; calculation of progression‑free survival, duration of response and overall survival; and measurement of changes from baseline in quality of life using the EORTC QLQ‑C30 and QLQ‑MY20 instruments.

The sponsor did not provide the total number of participants. The trial enrolled adult men and women (≥18 years) with a confirmed diagnosis of relapsed/refractory multiple myeloma according to IMWG criteria. Eligible subjects had received at least one prior line of therapy, including a lenalidomide‑containing regimen, and demonstrated disease progression. Inclusion required measurable disease, an ECOG performance status of 0–2, and either prior autologous stem cell transplant performed >100 days before first dose or transplant ineligibility. Participants also needed adequate hematologic, hepatic, and renal function and resolution of prior treatment‑related toxicities to ≤Grade 1 (except alopecia) or ≤Grade 2 peripheral neuropathy. Both genders were represented, and the population was considered vulnerable due to the advanced disease state. No specific lifestyle restrictions (e.g., diet or physical activity) were outlined in the available information.

The study is a phase II, multicenter, randomized, controlled interventional trial evaluating an MRD‑guided dosing strategy that compares reduced‑dose versus standard‑dose belantamab mafodotin in combination with pomalidomide and dexamethasone in adult patients with relapsed/refractory multiple myeloma. Participants are randomized 1:1 to one of the two dosing arms and receive treatment according to the assigned regimen throughout the study period, which spans from the estimated recruitment start on 15 June 2026 to the projected end date of 30 September 2033. The schedule of visits includes a screening visit for eligibility confirmation, baseline assessments, and initiation of therapy; regular treatment visits occurring every 3 weeks for drug administration and safety monitoring; MRD assessment visits at months 6, 12, 18, 24, 30, 36, and 42 to guide dose modifications; and a final end‑of‑study visit after the last dosing cycle or at study termination. Participant involvement therefore extends for up to 42 months of active treatment and follow‑up. Early discontinuation may occur in cases of disease progression, occurrence of grade 3 or higher treatment‑related adverse events that are not manageable, withdrawal of informed consent, or significant protocol non‑compliance.

Belantamab mafodotin is supplied as a powder for solution for injection intended for intravenous administration. The study protocol specifies a dose of 2.5 mg per kilogram of body weight. Each infusion is performed in the clinical setting according to the defined dosing schedule.

Pomalidomide is provided as hard capsules containing 4 mg of the active substance. The medication is taken orally and is administered in accordance with the protocol‑specified regimen. Compliance with oral dosing is monitored by capsule count at each study visit.

The trial compares a reduced‑dose regimen with the standard‑dose regimen of belantamab mafodotin, both administered in combination with oral pomalidomide and dexamethasone, reflecting a standard‑of‑care approach for relapsed/refractory multiple myeloma. Dosing schedules and adherence are documented by study personnel throughout the trial.

Efficacy will be evaluated using several disease‑specific endpoints. The primary efficacy parameter is Overall Response Rate (ORR), defined as the proportion of patients achieving at least a partial response according to International Myeloma Working Group (IMWG) criteria. Secondary efficacy parameters include the proportion of patients with minimal residual disease (MRD) less than 10⁻⁵ in bone marrow, sustained MRD negativity (two consecutive MRD‑negative results separated by ≥12 months), rates of complete response (CR) and very good partial response (VGPR) as per IMWG guidelines, duration of response (DOR), progression‑free survival (PFS), overall survival (OS), DOR in participants with CR‑MRD‑negative disease, and changes from baseline in quality of life measured with the EORTC QLQ‑C30 and QLQ‑MY20 questionnaires.

Response assessments are performed at predefined intervals throughout the study. MRD testing is scheduled at 6, 12, 18, 24, 30, 36, and 42 months after randomization. Quality‑of‑life questionnaires are administered at baseline and at regular study visits to capture longitudinal changes. All response evaluations, including ORR, CR, VGPR, and PR, are conducted using validated IMWG response criteria. MRD status is determined from bone‑marrow specimens using the study‑specified assay. Survival outcomes (PFS, OS) are calculated from the baseline date to the event of interest (disease progression, death, or last follow‑up). Duration of response is measured from the first documented response until disease progression or death. Data are analyzed using appropriate statistical methods for non‑inferiority comparison of the reduced‑dose regimen versus the standard dosing regimen.