DREAMM-9: Optimizing Belantamab Mafodotin Dosing in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

stable across cohorts due toTransplant-ineligible newly diagnosed multiple myeloma (TI NDMM) represents a population with distinct treatment needs, where balancing efficacy and tolerability is paramount. The DREAMM-9 trial (NCT04091126) was designed to address this challenge by evaluating belantamab mafodotin (belamaf, Blenrep; GlaxoSmithKline LLC) in combination with bortezomib, lenalidomide, and dexamethasone (BVRd) across a range of dosing schedules in adults with TI NDMM.

The data were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago.

The Fall and Rise of Belamaf

Belamaf was initially approved by the FDA in 2020, but was subsequently withdrawn from the market because the phase 3 DREAMM-3 confirmatory trial did not meet the requirements of the FDA Accelerated Approval regulations.² Despite the revoked approval, the agent remained accessible to patients through an expanded access program.¹

Its regulatory standing changed significantly in October 2025, when the FDA granted reapproval based on compelling data from the phase 3 DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) clinical trials. Both studies demonstrated meaningful improvements in median progression-free survival compared with daratumumab (Darzalex; Janssen Biotech, Inc), paving the way for belamaf's return to clinical use.¹

Investigating Belamaf in DREAMM-9

DREAMM-9 was a phase 1 dose and schedule evaluation study enrolling patients into 1 of 8 belamaf-dosing cohorts. Dosing schedules were organized by interval³:

• SHORT: Belamaf 1.9, 1.4, or 1.0 mg/kg, given every 3 weeks (induction) and every 4 weeks (maintenance)
• STRETCH: Belamaf 1.9 or 1.4 mg/kg, given every 6 weeks (induction) and every 8 weeks (maintenance)
• Step-down: Belamaf given at a higher starting dose then reduced, administered every 9 weeks (induction; every 9W) and every 12 weeks (maintenance; every 12W)
• Belemaf 1.0 mg/kg every 12 weeks

The primary end point was safety. Secondary assessments included overall response rate, minimal residual disease negativity (MRD−) in patients achieving complete response or better (CR+), and patient-reported outcomes (PROs). Median dose intensities (mDIs) were calculated separately for induction and maintenance phases.³

Belemaf Led to High Response

Overall response rates were high across all cohorts, reaching 83% or greater regardless of dosing schedule—a finding that underscores the broad activity of the BVRd regimen. However, the depth of response varied meaningfully by induction dose intensity. Cohorts with higher induction mDIs achieved the deepest responses: pooled SHORT and STRETCH cohorts yielded CR+ and MRD− rates of approximately 75% and 55%, respectively, compared with 59% and 43% in the pooled every 9/12 weeks and every 12 weeks cohorts.³

Induction mDI generally decreased as planned dosing intervals lengthened, whereas maintenance mDI remained relatively consistent across cohorts because of dose modifications.³

Belamaf Treatment Favors Longer Dosing Intervals

Ophthalmic exam findings (OEFs)—a known class effect of belamaf—were closely monitored. Grade 2 or higher OEFs were more common in higher-intensity cohorts, occurring in 90% of pooled SHORT and STRETCH patients compared with 69% in the pooled Q9/12W and Q12W group.³

Grade 3 or 4 OEF rates followed a similar pattern. Notably, 5 of 8 cohorts had no belamaf discontinuations due to grade 3 or higher OEFs, which were limited to SHORT cohorts (1 patient each). Encouragingly, first grade 2 or greater OEFs resolved prior to end of treatment in 83% to 100% of patients across cohorts.³

Patient-reported vision-related function also favored longer dosing intervals. The every 9/12 weeks and every 12 weeks groups largely remained below the clinically meaningful VRF deterioration threshold across most time points, compared with the SHORT interval group—a meaningful distinction for patient quality of life.³

Looking Forward With Belamaf

DREAMM-9 offers important insights into optimizing belamaf-based therapy in TI NDMM. Higher induction dose intensity drives deeper responses, whereas longer maintenance intervals improve tolerability and preserve PROs without sacrificing efficacy. These findings support a dosing strategy that maximizes depth of response during induction and prioritizes tolerability during maintenance.

REFERENCES

1. Chui M, Allen E. Advancing myeloma care: the pharmacist’s role in safe and effective use of blenrep. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2026; March 25-27, 2026; New Orleans, LA

2. Blenrep withdrawal: What myeloma patients need to know. International Myeloma Foundation. November 23, 2022. Accessed May 27, 2026. https://www.myeloma.org/news-events/withdrawal-blenrep-us-market

3. Usmani SZ, Mielnik M, Alonso A, et al. DREAMM-9 final analysis: belantamab mafodotin (belamaf), bortezomib, lenalidomide, and dexamethasone (BVRd) for transplant-ineligible (TI) newly diagnosed multiple myeloma (NDMM). Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 7503