Belantamab-Based Therapy in Patients With High-Risk Clinical Features: A Case Series

1. Introduction: Patients with multiple myeloma and high-risk clinical features, including International Staging System (ISS) stage III disease, extramedullary involvement, functional high risk and plasma cell leukemia, have unfavorable outcomes even in the absence of recognized high-risk cytogenetic abnormalities. These patients frequently experience early treatment failure and represent a population with a substantial unmet therapeutic need. Belantamab mafodotin is a B-cell maturation antigen-targeted antibody-drug conjugate with demonstrated activity in relapsed or refractory multiple myeloma. We report the preliminary efficacy and safety of belantamab-containing therapy in patients with clinically high-risk plasma cell disorders.

2. Materials and Methods: This retrospective case series included seven patients with relapsed or refractory multiple myeloma or plasma cell leukemia who initiated a belantamab-containing regimen between January 7 and March 28, 2026. Demographic characteristics, disease subtype, ISS stage, extramedullary involvement, cytogenetic risk, previous treatment exposure, response, measurable residual disease status, dose modifications, supportive therapy, and adverse events were reviewed retrospectively. The objective was to describe the preliminary effectiveness and safety of belantamab-based therapy in patients with high-risk clinical characteristics.

3. Results: Patients were 42-66 years old; five were men and two were women. Disease subtypes included IgG kappa in three patients, IgD lambda in one, IgG lambda in one, kappa light-chain disease in one, and IgA kappa plasma cell leukemia in one. Six patients had ISS stage III disease at diagnosis, whereas ISS stage was unavailable for one patient. Two patients had extramedullary disease at diagnosis. None met the most recent IMS/IMWG criteria for high-risk cytogenetic disease. Belantamab-containing therapy was administered in the second line in six patients and in the third line in one. All patients were triple-class exposed, and six also met criteria for functional high-risk disease.

All seven patients achieved an objective response: two achieved partial response, two very good partial response, and three complete response. The overall response rate was 100%, with five patients (71.4%) achieving at least a very good partial response and three (42.9%) achieving complete response. Measurable residual disease negativity was documented in two patients. All remain free of progression at last follow up (June 2026). Two patients received intravenous immunoglobulin replacement because of serum IgG levels below 400 mg/dL. Keratopathy occurred in all patients: one developed grade 3 keratopathy, whereas the remaining events were grade 1-2. All patients required at least one extension of the dosing interval. Other adverse events included one grade 3 infection, one grade 3 thrombocytopenia, and one grade 1 elevation of hepatic transaminases.

4. Conclusions: Belantamab-containing therapy produced deep responses in this small series of triple-class-exposed patients with high-risk clinical features, including ISS stage III disease, extramedullary involvement, and plasma cell leukemia. Keratopathy was frequent and resulted in dosing-interval extensions in all patients, although only one grade 3 ocular event occurred. Longer follow-up is required to determine response durability, progression-free survival, and the impact of dose modifications.

This represent the largest real- world experience with Belantamab mafodotin in patients with multiple myeloma in México, obtained through a compassionate access program.