Extended Belantamab Mafodotin Dosing Eases Ocular Function in DREAMM-9

Extended dosing intervals of belantamab mafodotin-blmf (Blenrep) were associated with better-maintained vision-related function and lower rates of severe blurred vision in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), according to a patient-reported outcomes (PRO) analysis from the phase 1 DREAMM-9 trial (NCT04091126) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹ The analysis evaluated the impact of different belantamab mafodotin dosing regimens on ocular tolerability when the agent was combined with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (BVRd).

What did the vision-related PRO analysis show?

Vision-related functioning was generally maintained over time in the extended-interval dosing groups. Mean changes remained below the 12.5-point threshold considered a clinically meaningful decline in the every-6-to-8-week (Q6/8W), every-9-to-12-week (Q9/12W), and every-12-week (Q12W) cohorts. A lower proportion of patients reported severe blurred vision in the cohorts with extended dosing intervals than in shorter-interval cohorts.

Severe blurred vision was reported by 67% to 92% of patients across the every-3-to-4-week (Q3/4W) cohorts, 58% in the Q6/8W cohorts, and 25% to 32% in the Q9/12W and Q12W cohorts. Similarly, interference with usual or daily activities due to blurred vision was reported by 75% to 82% of patients in the Q3/4W cohorts, 45% in the Q6/8W cohorts, and 25% to 33% in the Q9/12W and Q12W cohorts.

What ocular and efficacy context underlies the analysis?

Ocular events with belantamab mafodotin were common but generally transient and resolved across cohorts; grade 3 or higher events were less frequent in the cohorts with extended dosing intervals. Efficacy, reported previously, was robust across all dosing cohorts, with overall response rates of 90% in the Q3/4W group, 96% in the Q6/8W group, and 85% in the Q9/12W and Q12W group, and complete response or better rates of 68%, 88%, and 59%, respectively. The investigators noted a clear balance between efficacy and ocular tolerability, in which higher belantamab mafodotin dose intensity appeared important for achieving deep responses, while lower dose intensity and longer dosing intervals were associated with improved ocular tolerability.

“Taken altogether, there is a clear balance between efficacy vs ocular toxicity when it comes to belantamab mafodotin dosing, even though high rates and depth of response were seen in all dosing cohorts. The ocular events were common but were generally transient and resolved, and there were less severe events and less impact on functioning and daily activities with a lower belantamab mafodotin dosing interval and longer dosing interval,” study investigator Hang Quach, MBBS, FRACP, FRCPA, MD, professor of hematology at the University of Melbourne in Australia and departmental head of clinical hematology and clinical hematology research at St Vincent’s Hospital Melbourne, stated in a presentation of these data. “This does support an induction followed by a maintenance strategy with belantamab mafodotin dosing to maintain intensity initially and then extending the dose interval later on to improve tolerability.”

What is the DREAMM-9 design, and how were vision outcomes measured?

DREAMM-9 is a phase 1 dose- and schedule-evaluation study of belantamab mafodotin plus BVRd in adults with transplant-ineligible NDMM, for which efficacy and safety results were previously reported.² The trial evaluated belantamab mafodotin at doses of 1.0 to 1.9 mg/kg across dosing intervals ranging from every 3 or 4 weeks to every 12 weeks, with induction given alongside a bortezomib-containing standard-of-care regimen and maintenance with lenalidomide and dexamethasone.

Vision-related functioning was assessed using the Ocular Surface Disease Index, and blurred vision severity and its interference with daily activities were assessed using PRO-CTCAE scores, with measures collected at cycle 1 and at fixed intervals through treatment and at the end of treatment.

What is the significance of these findings?

The investigators concluded that the PRO results provide evidence that extended dosing schedules for belantamab mafodotin regimens support the maintenance of health-related quality of life in patients with transplant-ineligible NDMM. A strategy of belantamab mafodotin at 1.9 mg/kg every 8 weeks for 24 weeks followed by every-12-week dosing—maintaining dose intensity during induction and then extending the interval to improve tolerability—is being used in the ongoing phase 3 DREAMM-10 (NCT06679101) and PrE1005 (NCT07285239) studies.

References

1. Usmani SZ, Mielnik M, Abdallah AO, et al. DREAMM-9 patient-reported vision-related function with extended belantamab mafodotin dosing intervals with bortezomib, lenalidomide, dexamethasone (BVRd) in transplant ineligible multiple myeloma. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract OA-20.
2. Study of belantamab mafodotin plus standard of care (SoC) in newly diagnosed multiple myeloma (DREAMM 9). ClinicalTrials.gov. Updated November 28, 2025. Accessed September 28, 2026. https://tinyurl.com/cxsbnfcd