Belantamab Mafodotin Plus Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Key Clinical Summary: 

• Design/Population: The phase 1/2 DREAMM-6 study evaluated belantamab mafodotin in combination with bortezomib and dexamethasone across multiple dosing regimens in 107 heavily pretreated patients with relapsed/refractory multiple myeloma.
• Key Outcomes:  The overall response rate was 70%, with no dose-limiting toxicities observed. Ocular toxicity was common, with keratopathy and vision-related events reported in most patients.
• Clinical Relevance: Belantamab mafodotin-based combination therapy provides a potential treatment option for multiple myeloma. The 2.5 mg/kg every-3-week regimen appears to balance efficacy and safety, although ocular monitoring remains essential.

Results from the DREAMM-6 trial, Arm B, demonstrated that belantamab mafodotin plus bortezomib and dexamethasone shows strong clinical promise with manageable safety among heavily pretreated patients with relapsed/refractory multiple myeloma.

In this study, 107 adult patients were enrolled into 2 sequential dose-escalation cohorts to receive 2.5 mg/kg of belantamab mafodotin followed by 3.4 mg/kg every 3 weeks, in combination with bortezomib (twice weekly) and dexamethasone (4 times weekly). Primary end points included dose-limiting toxicities, safety, and objective response rate (ORR).

Additional patients were enrolled sequentially into 8 dose-expansion cohorts to receive belantamab mafodotin at 1.9 mg/kg, 2.5 mg/kg, or 3.4 mg/kg every 3 weeks; 2.5 mg/kg or 3.4 mg/kg every 3 weeks administered as split dosing (days 1 and 8); 1.9 mg/kg 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, all in combination with bortezomib and dexamethasone. 

At analysis, no dose-limiting toxicities were reported during dose escalation. The most frequently reported grade 3/4 adverse event was keratopathy, occurring in 53% of patients. Protocol-defined ocular events were reported in 93% of patients, with grade 3/4 events occurring in 77% of patients. Treatment-related serious adverse events occurred in 26% of patients, including 3 treatment-related deaths among 7 fatal serious adverse events.

The ORR was 70%. Exposure-response analyses suggested that higher initial drug exposure was associated with increased response as well as a higher incidence of ocular toxicity. Lower exposure regimens were associated with fewer deep responses, with only modest differences in ocular event rates.

“[Belantamab mafodotin combined with bortezomib and dexamethasone] demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated [relapsed/refractory multiple myeloma],” concluded study authors. 

These results “support the 2.5 mg/kg [once every 3 weeks] dose,” they noted. 

Source: 

Popat R, Augustson B, Cannell P, et al. Efficacy and safety of belantamab mafodotin with bortezomib plus dexamethasone in patients with relapsed/refractory multiple myeloma: The DREAMM-6 arm B trial. Clin Cancer Res. Published online: March 2, 2026. doi: 10.1158/1078-0432.CCR-25-3216