Belantamab Mafodotin Regimen Shows Activity in Transplant-Ineligible NDMM

Combining belantamab mafodotin-blmf (Blenrep) with lenalidomide (Revlimid) and dexamethasone (BelaRd) appeared highly active in patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for transplant, according to data from a phase 1/2 study (NCT04808037) published in Blood.¹

Among patients who received 1.9 mg/kg of belantamab mafodotin every week in group A (n = 15) and group B (n = 15), the objective response rate (ORR) was 96.7% (n = 29/30) across both groups, which included stringent complete responses (CRs) in 43.3% (n = 13), CRs in 10.0% (n = 3), very good partial responses (VGPRs) in 33.3% (n = 10), and partial responses in 3.3% (n = 1). The median progression-free survival (PFS) and overall survival (OS) were not yet reached, although the 18-month PFS rates were 86.7% (95% CI, 56.4%-96.5%) in group A and 71.4% (95% CI, 40.6%-88.2%) in group B.

Among 42 patients who received belantamab mafodotin at 1.9 mg/kg in both parts 1 and 2 of the study, data showed an 18-month PFS rate of 82.9% (95% CI, 67.5%-91.5%) and an 18-month time to progression (TTP) rate of 97.2% (95% CI, 81.9%-99.6%). After a median follow-up of 28.8 months, the 24-month PFS rates were 89.3% (95% CI, 63.2%-97.2%) for patients who received a dose of belantamab mafodotin below a median dose intensity of 0.605 mg/kg every 4 weeks and 64.6% (95% CI, 39.7%-81.34%) for those who received treatment below the median.

“The BelaRd study demonstrated that a [belantamab mafodotin] dose of 1.9 mg/kg every 8 weeks with lenalidomide and dexamethasone is highly active in [transplant-ineligible] patients with NDMM,” lead study author Evangelos Terpos, MD, PhD, from the Department of Clinical Therapeutics in the School of Medicine at National and Kapodistrian University of Athens, wrote with coauthors in the publication.¹ “Importantly, no drug administration enabled by the clinician using the vision-related anamnestic [VRA] instrument was contraindicated by the ophthalmologic assessment, whereas the schedule of every 8 weeks had minimal impact on daily activities, including reading and driving. Therefore, we advocate for a clinician-based, VRA-driven [belantamab mafodotin] administration supplemented by an ophthalmologic assessment only at baseline and when needed thereafter.”

Investigators of the open-label phase 1/2 study assessed the safety, tolerability, and activity of BelaRd among patients with transplant-ineligible NDMM across 2 distinct parts. In part 1 of the study, patients were randomly assigned 1:1:1 to receive belantamab mafodotin at 2.5 mg/kg (n = 12), 1.9 mg/kg (n = 12), or 1.4 mg/kg (n = 12) every 8 weeks in combination with lenalidomide and dexamethasone. In part 2 of the study, all patients received the recommended phase 2 dose of 1.9 mg/kg every 8 weeks but were randomly assigned to receive dosing guided by ophthalmologist-assessed ocular adverse events (OAEs) in group A (n = 15) or dosing guided by VRA tool-assisted and ophthalmologist-assessed grade 3 or higher OAEs in group B (n = 15).

The study’s primary end points included safety and tolerability based on dose-limiting toxicities, AEs, and serious AEs in part 1 as well as investigator-assessed ORR in part 2. Secondary end points included time to response, duration of response, PFS, and OS. Patients 18 years and older with transplant-ineligible NDMM based on International Myeloma Working Group (IMWG) frailty index scores of 1 or 2 and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial.

OAEs were the most frequently reported toxicity in part 1 of the study, as 97.2% (n = 35/36) experienced ocular symptoms. In the 2.5 mg/kg, 1.9 mg/kg, and 1.4 mg/kg cohorts, respectively, data revealed ocular toxicities at grade 1 (8.3%, 0%, 8.3%), grade 2 (8.3%, 41.7%, 58.3%), grade 3 (66.7%, 58.3%, 33.3%), and grade 4 (8.3%, 0%, 0%).

The safety profile in part 2 was comparable with that of part 1. All patients (100%) experienced OAEs in this part of the trial. In groups A and B, respectively, OAEs occurred at grade 1 (0% vs 6.7%), grade 2 (53.3% vs 73.3%), grade 3 (40.0% vs 13.3%), and grade 4 (6.7% vs 6.7%). Overall, less than 1% of patients stopped reading or driving due to OAEs.

“The study concluded that BelaRd is an effective regimen for patients [with transplant-ineligible NDMM], with OAEs having a limited impact on quality of life. The implementation of the hematologist-led VRA tool may reduce the necessity for ophthalmologist assessments and serve as a pragmatic approach for community practice,” Saad Z. Usmani, MD, MBA, FACP, FASCO, stated in a written commentary regarding these findings.² “These data were used to inform an international, multicenter, randomized phase 3 clinical trial [NCT04808037] in patients with [transplant-ineligible] NDMM, comparing [BelaRd] with daratumumab [Darzalex], lenalidomide, and dexamethasone, which is actively accruing patients. While we await further results—and acknowledging the caveat that [antibody drug conjugates] are new to [multiple myeloma] compared to other cancers—this drug class may become a valuable tool in the clinician’s therapeutic armamentarium.”

Usmani is a multiple myeloma specialist, cellular therapist, and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center. He is also a member of the International Myeloma Foundation’s Scientific Advisory Board.

References

1. Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, et al. Belantamab mafodotin, lenalidomide, and dexamethasone for intermediate-fit and frail patients with newly diagnosed myeloma. Blood. 2026;147(14):1574-1583. doi:10.1182/blood.2025031629
2. Usmani SZ. Breaking new ground with antibody-drug conjugates in myeloma. Blood. 2026;147(14):1510-1511. doi:10.1182/blood.2025032443