Efficacy and Safety of Belantamab Mafodotin with Bortezomib plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: The DREAMM-6 Arm B Trial

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: ORR 70% in heavily pretreated RRMM (median 4 prior therapies)

• Primary Outcome: Overall response rate 70% across all dosing cohorts

• Nnt Or Sensitivity: NNT approximately 1.4 for achieving response in this heavily pretreated population

• Confidence Interval: 95% CI: 60.5-78.6%

Clinical Application

Requires specialised haematology/oncology centres with experience in managing ocular toxicity and access to ophthalmology support Belantamab mafodotin requires TGA approval and PBS listing; combination builds on established bortezomib/dexamethasone backbone available in Australian practice Adults with relapsed/refractory multiple myeloma after multiple prior therapies, particularly those with limited treatment options

Abstract

PURPOSE: The phase I/II DREAMM-6 arm B study (NCT03544281) explored belantamab mafodotin combined with bortezomib/dexamethasone (BVd) in relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Adults with RRMM were enrolled sequentially in two belantamab mafodotin (intravenous) dose-escalation (DE) cohorts (2.5 then 3.4 mg/kg every 3 weeks). Additional patients enrolled sequentially to eight dose-expansion cohorts: 1.9, 2.5, or 3.4 mg/kg every 3 weeks; 2.5 or 3.4 mg/kg every 3 weeks split dose (days 1 and 8); 1.9 or 2.5 mg/kg every 6 weeks; or 2.5 mg/kg in cycle 1 stepped down to 1.9 mg/kg every 6 weeks thereafter. Patients received bortezomib twice weekly and dexamethasone four times weekly. Endpoints were dose-limiting toxicities (DLT; DE), adverse events (AE), serious AEs (SAE; DE and expansion), overall response rate (ORR; expansion), and pharmacokinetics. RESULTS: One hundred seven patients (median 4 prior lines of therapy) received BVd (n = 12-18/cohort). The median follow-up was 15.2 to 25.4 months. No DLTs occurred during DE. The most common grade 3/4 AE was keratopathy (53%). Protocol-defined ocular events (change in best corrected visual acuity and/or corneal examination findings) were reported in 93% of patients (grade 3/4: 77%). Twenty-eight (26%) patients experienced any study treatment-related SAEs; 3 of 7 fatal SAEs had a treatment-related primary cause. The ORR was 70% (95% confidence interval, 60.5-78.6). Higher initial exposures had higher probabilities of response and ocular events; lower exposures resulted in fewer deep responses, with small differences in ocular events. CONCLUSIONS: BVd demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated RRMM, supporting the 2.5 mg/kg every 3 weeks dose.

References

1. 1.Popat, R., Augustson, B., Cannell, P., Stockerl-Goldstein, K., Spencer, A., Khot, A., Nooka, A., Patel, N., Kasinathan, R. S., McKeown, A., Curry, A., Rogers, R., Shaikh, M., Carreno, F., Roy-Ghanta, S., Opalinska, J., & Quach, H. (2026). Efficacy and Safety of Belantamab Mafodotin with Bortezomib plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: The DREAMM-6 Arm B Trial. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-3216