Belantamab Mafodotin–Based Combos Win Japanese Approval for R/R Myeloma

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Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved belantamab mafodotin (Blenrep) in combination with bortezomib (Velcade) and dexamethasone (Vd) and in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy.1

The regulatory decision was supported by data from the phase 3 DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials, which evaluated belantamab mafodotin in combination with Vd and Pd, respectively.

“Today’s approval brings the benefits of [belantamab mafodotin] combinations to patients with relapsed or refractory multiple myeloma in Japan,” Hesham Abdullah, senior vice president of Global Head Oncology, R&D, at GSK, stated in a news release. “Patients need additional treatment options at or after first relapse that can extend remission and survival vs standard of care. [Belantamab mafodotin] combinations have the potential to redefine treatment outcomes based on superior efficacy shown in two phase 3 trials, with the added advantage of in-office administration in both academic and community treatment settings.”

In November 2024, the FDA accepted a biologics license application (BLA) seeking the approval of belantamab mafodotin in combination with Vd and Pd, respectively, for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy.2 The BLA was also supported by findings from DREAMM-7 and DREAMM-8.

DREAMM-7 Background

DREAMM-7 enrolled patients at least 18 years of age with a confirmed diagnosis of multiple myeloma per International Myeloma Working Group (IMWG) criteria who received at least 1 prior line of therapy and had documented disease progression during or after their most recent therapy.3 Other key inclusion criteria comprised an ECOG performance status of 0 to 2; at least 1 aspect of measurable disease; resolution of all prior treatment-related toxicities to grade 1 or less at the time of enrollment, other than alopecia; and adequate organ function. Patients could not be refractory to daratumumab (Darzalex) or any other anti-CD38 therapy.

A total of 494 patients were randomly assigned 1:1 to belantamab mafodotin at 2.5 mg/kg once every 3 weeks in combination with Vd or daratumumab plus Vd.1

Progression-free survival (PFS) per independent review committee assessment served as the trial’s primary end point. Secondary end points included overall survival (OS), duration of response (DOR), minimal residual disease (MRD)–negativity rate, overall response rate (ORR), safety, patient-reported outcomes (PROs), and quality of life (QOL).

Data from the multicenter, open-label, randomized DREAMM-7 study showed that belantamab mafodotin plus Vd (n = 243) produced a median PFS of 36.6 months compared with 13.4 months for daratumumab plus Vd (n = 251; HR, 0.41; 95% CI, 0.31-0.53; P < .00001).1 Additionally, at a median follow-up of 39.4 months, the combination of belantamab mafodotin and Vd generated a statistically significant and clinically meaningful improvement in OS, reducing the risk of death by 42% (HR 0.58; 95% CI: 0.43-0.79; P = .00023). The 3-year OS rates were 74% for belantamab mafodotin plus Vd vs 60% for daratumumab plus Vd.

DREAMM-8 Overview

In this multicenter, open-label, randomized trial, enrolled patients needed to have a confirmed diagnosis of multiple myeloma per IMWG criteria; prior receipt of at least 1 line of therapy, including lenalidomide (Revlimid); and documented disease progression during or after their most recent therapy.4 Prior autologous stem cell transplant was required, unless patients were considered transplant ineligible. Other key inclusion criteria included an ECOG performance status of 0 to 2 and adequate organ function.

Eligible patients were randomly assigned 1:1 to receive belantamab mafodotin at 2.5 mg/kg in the first cycle, then at 1.9 mg/kg every 4 weeks, plus Pd; or PVd.1

The primary end point was PFS per IRC assessment. Secondary end points comprised OS, MRD-negativity rate, ORR, DOR, safety, PROs, and QOL.

Findings from DREAMM-8 demonstrated that at a median follow-up of 21.8 months, patients treated with belantamab mafodotin plus Pd (n = 155) achieved a median PFS that was not yet reached (NR; 95% CI, 20.6-NR) compared with 12.7 months (95% CI, 9.1-18.5) for those given bortezomib plus pomalidomide and dexamethasone (PVd; n = 147; HR, 0.52; 95% CI, 0.37-0.73; P < .001). The 1-year PFS rates were 71% (95% CI, 63%-78%) and 51% (95% CI, 42%-60%), respectively. Although a statistically significant improvement in OS was not observed, a trend emerged favoring the belantamab mafodotin arm (HR, 0.77; 95% CI, 0.53-1.14).

Belantamab Mafodotin Safety Profile

Data from both studies showed that eye-related adverse effects associated with belantamab mafodotin were managed with extended time between infusions and dose reductions. Eye-related AEs led to treatment discontinuation in 9% of patients across the 2 studies. Changes in visual acuity resolved in 83% of instances, and no instances of permanent bilateral vision loss were reported.

The most common non-ocular AEs that occurred in more than 30% of patients treated with a belantamab mafodotin combination were thrombocytopenia (87%) and diarrhea (32%) in DREAMM-7, and neutropenia (63%), thrombocytopenia (55%) and COVID-19 (37%) in DREAMM-8.

References

1. Blenrep (belantamab mafodotin) combinations approved in Japan for treatment of relapsed/refractory multiple myeloma. News release. GSK. May 19, 2025. Accessed May 19, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-combinations-approved-in-japan/
2. Blenrep combinations accepted for review by the US FDA for the treatment of relapsed/refractory multiple myeloma. News release. GSK. November 25, 2024. Accessed May 19, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-combinations-accepted-for-review-by-the-us-fda-for-the-treatment-of-relapsedrefractory-multiple-myeloma/
3. Evaluation of efficacy and safety of belantamab mafodotin, bortezomib and dexamethasone versus daratumumab, bortezomib and dexamethasone in participants with relapsed/​refractory multiple myeloma (DREAMM 7). ClinicalTrials.gov. Updated October 24, 2024. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT04246047
4. Belantamab mafodotin plus pomalidomide and dexamethasone (Pd) versus bortezomib plus pd in relapsed/​refractory multiple myeloma (DREAMM 8). ClinicalTrials.gov. Updated March 18, 2025. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT04484623