Belantamab Mafodotin Regimen Yields Enduring Responses in NDMM

Combining belantamab mafodotin-blmf (Blenrep) with daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (BelaDRd) produced robust clinical activity among patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for transplant, according to findings from a phase 1/2 study (NCT05280275) presented at the European Hematology Association (EHA) 2026 Congress.¹

In part 1 of the study, 81.3% (n = 13/16) of evaluable patients achieved minimal residual disease (MRD) negativity for a median duration of 14.1 months and a median time to MRD negativity of 12.6 months. Among 7 evaluable patients in part 2 of the trial, 71.4% (n = 5/7) experienced MRD-negative status for a median duration of 6.3 months and a median time to MRD negativity of 10.7 months. Overall, high rates of MRD negativity with sustained disease control were reported across cohorts and groups.

The overall response rate (ORR) was 91.7% in parts 1 and 2 of the trial, with a median time to best response of 13.8 months and 10.2 months in each respective part. Additionally, a complete response (CR) or better was observed in 66.7% and 58.3% of each group; the median time to CR or better was 13.8 months and 11.7 months, respectively.

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%) among patients who received belantamab mafodotin at the recommended phase 2 dose (RP2D) of 1.9 mg/kg every 12 weeks. Across each population, the 18-month time to progression (TTP) rates were 97.1% (95% CI, 80.9%-99.6%) and 95.5% (95% CI, 71.9%-99.4%), respectively. Overall, investigators noted 2 TTP events;1 event after 24 months in part 1 and 1 event before 12 months in part 2.

Across different calculations, model-based median PFS estimates ranged from 78.7 months to 133.9 months, which suggested extended FPS with limited progression events reported to date.

“[BelaRd]…demonstrated rapid, deep, and durable responses with a high [ORR] and MRD negativity in this intermediate-fit and frail population of [patients with NDMM],” study investigator Evangelos Terpos, MD, PhD, from the Department of Clinical Therapeutics in the School of Medicine at National and Kapodistrian University of Athens, stated in the presentation. “[T]hese results [warrant] a phase 3 study studying this quadruplet combination.”

Although the MAIA trial (NCT02252172) previously established DRd as a preferred regimen for patients with NDMM, investigators hypothesized that combining belantamab mafodotin with DRd in an extended dosing schedule may further improve outcomes among patients.² They designed the 2-part, phase 1/2 trial to evaluate BelaDRd among patients with transplant-ineligible NDMM who intermediate fit or frail per International Myeloma Working Group (IMWG) criteria.

Initially, patients were randomly assigned to receive belantamab mafodotin at 1.9 or 1.4 mg/kg every 8 weeks in combination with DRd. After determining the RP2D of belantamab mafodotin, patients were subsequently randomly assigned to treatment guided by an ophthalmologist in group A (n = 8) or a hematologist in group B (n = 6).

The trial’s primary end points included dose-limiting toxicities in part 1, adverse effects (AEs) and serious AEs (SAEs) across parts 1 and 2, ocular toxicity in parts 1 and 2, and ORR in part 2.³ Secondary end points included TTR, duration of response, CR rate, and PFS.

Patients 18 years and older with documented multiple myeloma, ineligibility for high-dose chemotherapy with autologous stem cell transplantation (ASCT), an ECOG performance status of 0 to 2, and intermediate-fit or frail status per IMWG guidelines were eligible for enrollment on the trial. Having adequate organ function was another requirement for study entry.

The median patient age was 73.0 years (range, 64.0-84.0) in part 1 and 74.0 years (range, 65.0-80.0) in part 2; most patients in each part were male (54.2% vs 58.3%). Investigators noted high treatment continuation and consistent dose intensity across both groups.

Grade 3 or higher best corrected visual acuity decline was reported in 10.4% (n = 74) of ocular assessments in part 1 and 3.9% (n = 4) and 5.3% (n = 5) in groups A and B of part 2, respectively. Grade 2 or higher and grade 3 or higher keratopathy was noted in 6.7% and 0% of assessments in group A and 10.6% and 0% of assessments in group B. Most grade 2 or higher ocular events resolved to grade 1 or lower.

In part 1 of the study, assessments showing that patients stopped driving and reading due to eyesight issues were observed at rates of 1.0% (n = 6/611) and 0.5% (n = 3/725), respectively. Across 104 assessments among patients treated in group A of part 2, none indicated that patients stopped driving or reading due to ocular toxicity. Across 98 assessments gathered in part B, 1 evaluation indicated that a patient stopped driving due to eyesight issues.

References

1. Terpos E, Ntanasis-Stathopoulos I, Gavriatopoulou M, 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-DRdstudy. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S204.
2. Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
3. A study to investigate the safety and clinical activity of belantamab mafodotin in combination with daratumumab, lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma transplant ineligible. ClinicalTrials.gov. Updated December 1, 2023. Accessed June 15, 2026. https://tinyurl.com/4aj9w267