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

Popat, R; Augustson, B; Cannell, P; Stockerl-Goldstein, K; Spencer, A; Khot, A; Nooka, A; Patel, N; Kasinathan, RS; McKeown, A; Curry, A; Rogers, R; Shaikh, M; Carreno, F; Roy-Ghanta, S; Opalinska, J; Quach, H

Author(s): Popat, R; Augustson, B; Cannell, P; Stockerl-Goldstein, K; Spencer, A; Khot, A; Nooka, A; Patel, N; Kasinathan, RS; McKeown, A; Curry, A; Rogers, R; Shaikh, M; Carreno, F; Roy-Ghanta, S; Opalinska, J; Quach, H;
Details: Publication Year 2026-05-15,Volume 32,Issue #10,Page 1962-1972
Journal Title: Clinical Cancer Research
Publication Type: Research article
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.
Publisher: American Association for Cancer Research
Keywords: Humans; *Multiple Myeloma/drug therapy/pathology/mortality; Bortezomib/administration & dosage/adverse effects; Dexamethasone/administration & dosage/adverse effects; Male; Middle Aged; Female; Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; Adult; *Neoplasm Recurrence, Local/drug therapy/pathology; Drug Resistance, Neoplasm; Aged, 80 and over; Treatment Outcome; Antibodies, Monoclonal, Humanized
Department(s): Haematology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-25-3216
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-25-3216
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-31 11:33:32

Last Modified: 2026-05-28 05:49:00