Improved Outcomes in NDTE Multiple Myeloma With Belantamab Mafodotin Plus VRd Following 2 Years of Maintenance

Data from the GEM-BELA-VRd clinical trial (NCT04802356) demonstrate that, when added to bortezomib (Velcade; Takeda Pharmaceuticals), lenalidomide (Revlimid; Bristol Myers Squibb), and dexamethasone (VRd), belantamab mafodotin (belamaf; Blenrep; GSK) followed by continuous lenalidomide promotes deep responses in patients with newly diagnosed transplant-eligible multiple myeloma (NDTE-MM). These findings were presented at the 2025 International Myeloma Society Annual Meeting in Toronto, Canada.^1,2

Earlier results from GEM-BELA-VRd, a multicenter, open-label phase 2 clinical trial, showed that adding belamaf to VRd were encouraging. Specifically, 40 patients with NDTE-MM who had completed 4 induction cycles of treatment had high rates of deep responses, including complete responses (CRs) and minimal residual disease (MRD)–negativity. Of note, ocular events (Oes) were common, but they were generally reversible and manageable, according to findings published in Blood.^2,3

This current analysis includes 2-year data from the GEM-BELA-VRd trial.¹ Patients were treated with belamaf (2.5 mg/kg) intravenously (IV) every 8 weeks with VRd for 6 induction cycles, followed by autologous stem cell transplant (ASCT), 2 consolidation cycles with belamaf-VRd (2.5 mg/kg) every 8 weeks, and maintenance with continuous lenalidomide plus belamaf (1.9 mg/kg Q8W) for up to 2 years. The trial’s primary end point was safety, and secondary end points included CR, MRD–negativity, time to progression (TTP), progression-free survival (PFS), and overall survival (OS). Data cutoff was on April 28, 2025.^1,2

The median follow-up was about 40.0 months (range: 36.2–49.0 months), according to the investigators. In the intent to treat population (n = 50), the best objective response rate was approximately 96%, CR was 80%, and MRD–negativity was 88%. Additionally, in a per-protocol analysis, MRD–negativity was about 87.8% at the end of consolidation (n = 41), 91.9% after the first year of maintenance (n = 37), and 93.9% after the second year (n = 33).

At the final follow-up, only 3 patients had progressed, of which one occurred at 7 months, and 2 at 26 and 33 months, respectively, with a 3-year TTP (93%). Further, 10 patients died: 5 from infections (COVID-19: 4; sepsis: 1), 2 from progression, 1 from inflammatory colitis during induction, 1 unknown, and 1 unrelated, with a 3-year PFS of 78% and 3-year OS of 82%.¹

The investigators reported no new safety signals that emerged during the maintenance period. Of note, OEs were less frequent than in previous phases. All OEs resolved, with a median recovery time of about 75 days and full resolution in 175 days (range: 35–476 days), except in 3 patients with ongoing follow-up and improved best corrected visual acuity.¹

Grade 3 or higher neutropenia occurred in 36% of patients in the first year but decreased to 22% in the second year. Infections occurred in approximately 18% of patients in the first year and 8% in the second. Only 4 patients discontinued maintenance because of toxicity (cytopenias or infections), occurring in both years.¹

“Final analysis of this pilot study of belamaf-VRd followed by continuous [lenalidomide] plus up to 2 years of belamaf confirms deep responses in [patients with NDTE-MM], with high rates of CR and MRD–negativity. OEs and hematological [adverse events] were manageable and belamaf appeared not to add toxicity to [lenalidomide] maintenance. Infections, particularly COVID-19, had a notable impact on the trial, influencing outcomes and safety. These results support further evaluation of belamaf in the frontline setting,” the investigators concluded.¹

REFERENCES

1. González-Calle V, Puig N, Ocio E, et al. Final Analysis of the GEM-BELA-VRd Phase II Trial: Belantamab Mafodotin Plus VRd in Newly Diagnosed Transplant-Eligible Myeloma After 2 Years of Maintenance with Belantamab and Lenalidomide. Presented at: International Myeloma Society Annual Meeting. Toronto, Canada. September 17–20.

2. Belantamab Mafodotin in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients. ClinicalTrials.gov identifier: NCT04802356. Updated December 6, 2021. Accessed September 26, 2025. https://clinicaltrials.gov/study/NCT04802356

3. González-Calle V, Otero PR, Rey-Bua B, et al. Belantamab Mafodotin in Combination with Vrd for the Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Results from the Phase II, Open Label, Multicenter, GEM-BELA-Vrd Trial. Blood. 2022;140(Supplement 1):7286–7288. doi:10.1182/blood-2022-162584