Belantamab Mafodotin Combo Significantly Improves OS in Multiple Myeloma

The DREAMM-7 trial (NCT04246047) is one of the ongoing initiatives from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) program designed to assess treatment with belantamab mafodotin in early lines of multiple myeloma therapy.

Combining belantamab mafodotin (Blenrep) with bortezomib (Velcade) and dexamethasone significantly reduced the risk of death vs daratumumab (Darzalex) plus bortezomib/dexamethasone among patients with relapsed/refractory multiple myeloma, according to findings from the phase 3 DREAMM-7 trial (NCT04246047).¹

Second-line or later therapy with the belantamab mafodotin regimen reached the key secondary end point of overall survival (OS) in the DREAMM-7 trial. Investigators will present full results from the interim analysis, including data related to safety, at the 2024 ASH Annual Meeting and Exposition.

“The [OS] results from the DREAMM-7 trial underscore the potential for this [belantamab mafodotin] combination to extend the lives of patients with relapsed/refractory multiple myeloma,” Hesham Abdullah, senior vice president and global head of Oncology Research and Development at GSK, the developer of belantamab mafodotin, stated in a press release.¹ “This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment. We look forward to sharing these data with health authorities and presenting the full results at next month’s American Society of Hematology Annual Meeting.”

The DREAMM-7 trial is one of the ongoing initiatives from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) program designed to assess treatment with belantamab mafodotin in early lines of multiple myeloma therapy. Investigators are also evaluating belantamab mafodotin plus pomalidomide (Pomalyst) and dexamethasone vs bortezomib plus pomalidomide/dexamethasone as part of the phase 3 DREAMM-8 trial (NCT04484623). Additionally, developers anticipate launching a new phase 3 study of belantamab mafodotin in patients with newly diagnosed, transplant-ineligible multiple myeloma by the end of 2024.

In the open-label, multicenter phase 3 DREAMM-7 trial, 494 patients with previously treated relapsed/refractory multiple myeloma were randomly assigned 1:1 to receive belantamab mafodotin or daratumumab in combination with bortezomib/dexamethasone. Patients received belantamab mafodotin at 2.5 mg/kg intravenously every 3 weeks.

The trial’s primary end point is progression-free survival (PFS) based on independent review committee assessment. Secondary end points include OS, duration of response, minimal residual disease negativity, overall response rate, safety, patient-reported outcomes, and quality of life.

Patients 18 years and older with a confirmed diagnosis of multiple myeloma per International Myeloma Working Group criteria and evidence of disease progression on or after their most recent line of therapy were eligible for enrollment on the DREAMM-7 trial.² Additional eligibility criteria included having an ECOG performance status of 0 to 2, adequate organ function, and all prior treatment-related toxicities resolving grade 1 or lower at the time of enrollment.

Those with an intolerance of daratumumab, refractory disease following prior treatment with daratumumab or any other anti-CD38 therapy, intolerance of bortezomib, or ongoing grade 2 or higher peripheral neuropathy or neuropathic pain were ineligible for enrollment on the trial. Patients were also excluded if they had prior treatment with anti-BCMA agents, prior allogenic stem cell transplant, or corneal epithelial disease. Having any serious and/or unstable pre-existing medical or psychiatric disorders such as renal, liver, cardiovascular, or certain prior malignancies was also grounds for exclusion from enrollment.

In July 2024, the European Medicines Agency accepted a marketing authorization application for belantamab mafodotin in combination with bortezomib/dexamethasone or pomalidomide/dexamethasone for patients with relapsed/refractory multiple myeloma.³ Additionally, Japan’s Ministry of Health, Labour and Welfare accepted a new drug application for belantamab mafodotin in combination with the same agents in September 2024.⁴ Both applications were supported by findings from the DREAMM-7 trial and the DREAMM-8 trial.

References

1. Blenrep shows overall survival benefit in head-to-head DREAMM-7 phase III trial for relapsed/refractory multiple myeloma. News release. GSK. November 14, 2024. Accessed November 14, 2024. https://tinyurl.com/4zpxuk3m
2. 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 November 14, 2024. https://tinyurl.com/yk7m6vnh
3. Blenrep (belantamab mafodotin) combinations in multiple myeloma application accepted for review by the European Medicines Agency. News release. GSK. July 19, 2024. Accessed November 14, 2024. https://tinyurl.com/tzx6253t
4. Blenrep (belantamab mafodotin) combinations in relapsed/refractory multiple myeloma accepted for regulatory review in Japan. News release. GSK. September 17, 2024. Accessed November 14, 2024. https://tinyurl.com/3wu4w368