Belantamab Mafodotin/Bortezomib/Dexamethasone Yields PFS, OS Benefits in Lenalidomide-Refractory Myeloma

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The combination of belantamab mafodotin-blmf (Blenrep), bortezomib (Velcade), and dexamethasone (BVd) produced superior progression-free survival (PFS), sustained overall survival (OS) benefit, and favorable minimal residual disease (MRD) negativity rates vs standard daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd) in patients with multiple myeloma who were refractory to lenalidomide at first relapse, according to findings from a post-hoc analysis of the phase 3 DREAMM-7 trial (NCT04246047).1

Data presented during the 22nd Annual International Myeloma Society Meeting and Exposition showed that BVD produced clinically meaningful PFS, OS, and PFS2 benefits vs DVd. The median PFS was 35.7 months (95% CI, 17.5-not evaluable [NE]) with BVd (n = 21) vs 13.5 (95% CI, 6.6-26.3) with DVd (n = 27), translating to a HR of 0.39 (95% CI, 0.17-0.88). The 24-month PFS rates were 67% (95% CI, 41%-84%) and 35% (95% CI, 17%-53%) in these respective arms.

Furthermore, the median OS was not reached (NR; 95% CI, 35.7%-NE) with BVd vs 35.4 months (95% CI, 24.4-NE) with DVd (HR, 0.64; 95% CI, 0.26-1.59). The 24- and 36-month OS rates in the BVd arm were 79% (95% CI, 53%-92%) and 74% (95% CI, 48%-88%), respectively. In the DVd arm, these respective rates were 77% (95% CI, 55%-89%) and 50% (95% CI, 28%-68%).

“Treatment benefits with BVd were maintained after subsequent [treatment with] antimyeloma therapies…[and] the safety and tolerability of the BVd regimen were consistent with the primary analysis,” presenting author María-Victoria Mateos, MD, PhD, stated in a presentation of the data. “These results support the consideration of BVd as a new potential standard of care for lenalidomide-refractory patients with relapsed/refractory multiple myeloma and only 1 prior line of therapy, addressing a critical unmet need in this [patient] population.”

Mateos is a consultant physician and associate professor of medicine in the Hematology Department at the University of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC) in Spain.

What Clinical Need Does BVd Address in Lenalidomide-Refractory Multiple Myeloma?

In November 2024, the FDA accepted a biologics license application seeking the approval of BVd for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy, partly based on data from DREAMM-7.2

Prior findings from DREAMM-7, which were published in the New England Journal of Medicine, showed that at a median follow-up of 28.2 months (range, 0.1-40.0), the median PFS with BVd (n = 243) was 36.6 months (95% CI, 28.4-NR) vs 13.4 months (95% CI, 11.1-17.5) with DVd (n = 251; HR, 0.41; 95% CI, 0.31-0.53; P < .001).3

Investigators conducted a post hoc analysis to examine outcomes in the subgroup of patients from DREAMM-7 who were lenalidomide-refractory at first relapse.1

What Was the Design of the DREAMM-7 Trial Subgroup Analysis?

The randomized, open-label DREAMM-7 trial enrolled 494 patients 18 years of age and older with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy. Prior treatment with an anti-BCMA therapy or refractoriness to anti-CD38 therapy was not permitted, nor was disease that was refractory or intolerant to bortezomib.1,3,4

Eligible patients were randomly assigned 1:1 to receive the following regimens:

  • 2.5 mg/kg of intravenous (IV) belantamab mafodotin every 3 weeks in combination with bortezomib and dexamethasone for 8 cycles; belantamab mafodotin monotherapy in cycle 9 and beyond
  • 16 mg/kg of IV belantamab mafodotin weekly during cycles 1 to 3 and every 3 weeks in cycles 4 to 8 in combination with bortezomib and dexamethasone for 8 cycles; daratumumab monotherapy in cycle 9 and beyond

Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of consent, or study conclusion.

The trial’s primary end point was PFS. Secondary end points included OS, duration of response (DOR), and MRD negativity.3 Post hoc analyses of PFS, OS, PFS2, overall response rate (ORR), MRD, and DOR were performed in patients who had received at least 1 prior line of therapy and were refractory to lenalidomide.1

Were Patient Characteristics Balanced Between the BVd and DVd Arms at Baseline in the DREAMM-7 Post Hoc Analysis?

The data cutoff for the current analysis was October 7, 2024. Baseline characteristics were generally balanced across arms. The median age was 65.0 years (range, 34-86) in the BVd arm and 67.0 years (range, 45-81) in the DVd arm. Most patients in both arms were male (73% in BVd arm; 74% in DVd arm), were White (100%; 78%), had standard-risk cytogenetics (73%; 70%), and did not display extramedullary disease (91%; 96%). At screening, 50% vs 37% of patients in the BVd and DVd arms, respectively, had R-ISS stage I disease; 45% vs 59% of patients had stage II disease; and 5% vs 4% of patients had stage III disease.

Seven and 13 patients from the BVd and DVd arms, respectively, went on to receive subsequent antimyeloma therapy. This included:

  • Steroids: 29% vs 37%
  • Immunomodulators: 29% vs 33%
  • Proteasome inhibitors: 19% vs 30%
  • Chemotherapy: 19% vs 15%
  • Monoclonal antibodies: 24% vs 7%
  • Antibody-drug conjugates: 5% vs 11%
  • Bispecific antibodies: 0% vs 7%
  • Engineered T-cell or natural killer–cell therapy: 0% vs 4%
  • Other therapy: 5% vs 4%

Of note, information on subsequent therapy was missing for 10% of patients in the BVd arm.

What Were the PFS2, Response, and MRD Negativity Rates with BVd vs DVd?

PFS2 benefit was maintained with BVd followed subsequent treatment with antimyeloma therapies. The median PFS2 with BVd was NR (95% CI, 29.0-NE) vs 29.3 (95% CI, 13.8-NE) with DVd (estimated HR, 0.66; 95% CI, 0.27-1.59).

BVd also led to high rates of MRD negativity and deep, durable responses in this patient population. The respective response rates for BVd and DVd were as follows:

  • BVd: ORR, 95.2% (95% CI, 76.2%-99.9%)
    • 14.3% stringent complete response (sCR; n = 3); 42.9% CR (n = 9); 23.8% very good partial response (VGPR; n = 5); 14.3% PR (n = 3)
  • DVd: ORR, 81.5% (95% CI, 61.9%-93.7%)
    • 11.1% sCR (n = 3); 14.8% CR (n = 4); 40.7% VGPR (n = 11); 14.8% PR (n = 4)

The median DOR with BVd was NR (95% CI, 16.2-NE) vs 13.1 months (95% CI, 7.0-NE) with DVd. The 24-month DOR rates were 65% (95% CI, 38.0%-82.0%) and 36% (95% CI, 17.0%-56.0%) with these respective regimens.

A CR or higher and MRD negativity were achieved by 38.1% (95% CI, 18.1%-61.6%) of patients in the BVd arm vs 7.4% (95% CI, 0.9%-24.3%) of patients in the DVd arm; the MRD negativity rates in patients with a CR or greater were 67% and 29%, respectively. A VGPR or greater and MRD negativity were achieved by 57.1% (95% CI, 34.0%-78.2%) of patients in the BVd arm and 22.2% (95% CI, 8.6%-42.3%) of patients in the DVd arm; respective MRD negativity rates among those patients with a VGPR or greater were accordingly 71% and 33%.

Was the Safety Profile of BVd Consistent with Prior Findings in This Patient Population?

No new safety concerns were reported with BVd or DVd in the post hoc analysis. All patients across both arms experienced adverse effects (AEs) of any grade, 100% of which were related to any study treatment. Grade 3 or 4 AEs were reported in 100% of patients in the BVd arm and 78% of those in the DVd arm; of these, 100% and 70% were deemed treatment related, respectively.

AEs led to permanent discontinuation of any study drug in 29% and 15% of patients in the BVd and DVd arms, respectively. All 29% of patients in the BVd arm who discontinued treatment did so due to AEs related to the study drug, vs 11% of those in the DVd arm. Patients also experienced AEs leading to dose reduction (71% vs 56%) and dose interruption or delay (95% vs 78%).

Any-grade serious AEs (AEs) were reported in 62% and 41% of patients in the BVd vs DVd arms, respectively; of these, 29% and 15% were related to the study drug. Fatal serious AEs occurred in 5% of patients in the BVd arm and 7% of patients in the DVd arm; none of these effects were deemed related to study treatment.

References

  1. Hungria V, Robak P, Hus M, et al. Outcomes in second-line lenalidomide-refractory patients in the phase 3 DREAMM-7 study of belantamab mafodotin, bortezomib (V), and dexamethasone (d) vs daratumumab-Vd in RRMM. Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract PA-494.
  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 September 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. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090
  4. 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, 2025. Accessed September 19, 2025. https://clinicaltrials.gov/study/NCT04246047

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