Belantamab Mafodotin Combo Yields High MRD Negativity in NDMM

Belantamab mafodotin-blmf (Blenrep) combined with daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (Bela-DRd) produced rapid, deep, and durable responses with high rates of measurable residual disease (MRD) negativity in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), according to results from the phase 1/2 Bela-DRd study (NCT05280275) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.

In the part 1 dose-finding phase (n = 24), the overall response rate (ORR) was 91.7% (n = 22/24), with 66.7% of patients achieving a complete response (CR) or better. MRD negativity was achieved in 13 of 16 evaluable patients (81.3%) and sustained at 12 months in 9 patients (69.2%). In the part 2 dose-expansion phase (n = 12), the ORR was 91.7% (n = 11/12), with 58.3% achieving a CR or better, and MRD negativity was achieved in 5 of 7 evaluable patients (71.4%). The median time to a partial response or better was 1.1 months.

The 18-month progression-free survival (PFS) rate was 91.7% (95% CI, 76.4%-97.2%) in the overall population and 87.5% (95% CI, 66.1%-95.8%) in the recommended phase 2 dose (RP2D) population. The 18-month overall time to progression (TTP) rate was 97.1% (95% CI, 80.9%-99.6%). Model-based estimates projected a median PFS ranging from 78.7 to 133.9 months (approximately 6.5-11 years), suggesting prolonged disease control with limited progression events observed to date.

Ocular toxicity, a known effect of belantamab mafodotin, was mostly low grade and consistent across the two part 2 dosing-management strategies. In part 2, grade 3 or higher best-corrected visual acuity (BCVA) decline occurred in 4.5% of ocular assessments, and no grade 3 or higher keratopathy was observed. Among grade 2 or higher ocular adverse events (AEs), BCVA events resolved in 87.5% of cases (median time to resolution, 1.9 months), and keratopathy events resolved in 91.6% of cases (median, 1.0 month).

Belantamab mafodotin doses were skipped because of ocular AEs in 27.6% of planned doses in part 1 and 11.5% in part 2; in the hematologist-guided group, only 2 dose skips were recorded. Almost all patients were able to continue daily activities such as driving and reading.

“The combination of belantamab mafodotin with lenalidomide, dexamethasone, and daratumumab, given every 2 to 3 months, demonstrated rapid and durable responses with an MRD negativity rate of 81%, which was sustained in 70% of the patients in a patient population which included intermediate-fit and frail, newly diagnosed symptomatic patients with [multiple] myeloma,” said lead investigator Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Alexandra Hospital, in Athens, Greece, in his concluding remarks. “I believe that this is an active combination which competes, quote unquote, with quadruplets and also with other very active combinations that we are seeing in [multiple] myeloma.”

Bela-DRd is an open-label, phase 1/2 study in patients with NDMM who are ineligible for high-dose chemotherapy with autologous stem cell transplant and are intermediate-fit or frail according to the International Myeloma Working Group (IMWG) frailty score. In part 1, 24 patients were randomly assigned 1:1 to belantamab mafodotin at 1.9 mg/kg (cohort 1) or 1.4 mg/kg (cohort 2) every 8 weeks, each combined with subcutaneous daratumumab at 1800 mg every 4 weeks, lenalidomide at 25 mg on days 1 to 21, and dexamethasone at 40 mg on days 1, 8, 15, and 22. Belantamab mafodotin at 1.9 mg/kg every 8 weeks, extended to every 12 weeks, was selected as the RP2D.

In part 2, 12 patients were randomly assigned 1:1 to receive the RP2D with ocular dose modifications guided either by an ophthalmologist (group A, n = 6) or by a hematologist using the Vision-Related Anamnestic (VRA) tool (group B, n = 6). Patients had a median age of 73 to 74 years, and all were elderly and intermediate-fit or frail. The study was conducted at Alexandra Hospital in Athens, Greece.

The coprimary end points of part 1 were the safety and tolerability of Bela-DRd and determination of the belantamab mafodotin RP2D; the coprimary end points of part 2 were efficacy (ORR per IMWG criteria) and safety, including grade 2 or higher ocular toxicity. Secondary end points included PFS, TTP, overall survival, MRD negativity, and ocular AE incidence and management.

In part 2, ophthalmologist assessments did not alter the hematologist’s treatment decisions, supporting the feasibility of hematologist-guided ocular management with the VRA tool. The investigators concluded that Bela-DRd, with belantamab mafodotin administered every 2 to 3 months, demonstrated robust clinical activity with rapid, deep responses and high MRD negativity rates alongside manageable toxicity.

Reference

Dimopoulos MAC, Gavriatopoulou M, Ntanasis-Stathopoulos I, et al. High MRD negativity rates and prolonged PFS with belantamab mafodotin plus daratumumab, lenalidomide, and dexamethasone in transplant ineligible newly-diagnosed myeloma: results of the Bela-DRd study. Presented at: 2026 European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. Abstract 1454O.