Belantamab Mafodotin Plus Bortezomib/Dexamethasone Extends OS in R/R Myeloma

Belantamab mafodotin-blmf (Blenrep) in combination with bortezomib (Velcade) and dexamethasone demonstrated a statistically significant and clinically meaningful reduction in the risk of death compared with daratumumab (Darzalex) plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma, meeting the key secondary end point of overall survival (OS) in the phase 3 DREAMM-7 trial (NCT04246047).¹

Full data from the interim analysis of DREAMM-7 will be presented during the 2024 ASH Annual Meeting on December 9, 2024. The DRiving Excellence in Approaches to Multiple Myeloma (DREAMM) clinical development program is evaluating belantamab mafodotin in early lines of treatment and in combination with novel and standard of care therapies. The phase 3 DREAMM-8 trial (NCT04484623) is examining belantamab mafodotin plus pomalidomide (Pomalyst) and dexamethasone in patients with relapsed/refractory multiple myeloma.

“The OS results from the DREAMM-7 trial underscore the potential for this belantamab mafodotincombination to extend the lives of patients with relapsed/refractory multiple myeloma,” Hesham Abdullah, MD, MSc, senior vice president, Global Head Oncology, Research & Development, GSK, stated in a news release. “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 ASH Annual Meeting.”

Data from DREAMM-7 and DREAMM-8 have supported regulatory filings in the US, European Union, Japan, United Kingdom, Canada, and Switzerland for the treatment of patients with relapsed/refractory multiple myeloma. Additionally, China’s National Medical Products Administration granted breakthrough therapy designation to belantamab mafodotin plus bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma and priority review for regulatory approval, both supported by findings from DREAMM-7.

DREAMM-7 was an open-label, global study that examined belantamab mafodotin plus bortezomib and dexamethasone vs daratumumab plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma following at least 1 prior line of therapy; disease progression was required during or after their most recent treatment.2 Patients were excluded from the study if they were refractory to anti-CD38 therapy or had had prior exposure to anti-BCMA therapy.

Eligible patients were randomly assigned 1:1 to receive intravenous (IV) belantamab mafodotin at 2.5 mg/kg on day 1 of each 21-day cycle or IV daratumumab at 16 mg/kg weekly in cycles 1 through 3, every 3 weeks during cycles 4 through 8, and every 4 weeks in cycle 9 and beyond. Patients in both arms also received subcutaneous bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11, and dexamethasone20 mg on the day of and the day after bortezomib for the first 8 cycles. Treatment with belantamab mafodotin or daratumumab continued until disease progression, unacceptable toxicity, patient withdrawal, or death.

The primary end point was progression-free survival (PFS). Key secondary end points consisted of OS, duration of response (DOR), and minimal residual disease (MRD) negativity.

At a median follow-up of 28.2 months (range, 0.1-40.0), prior data from DREAMM-7 published in The New England Journal of Medicine demonstrated that patients in the belantamab mafodotin arm (n = 243) achieved a median PFS of 36.6 months (95% CI, 28.4–not reached [NR]) compared with 13.4 months (95% CI, 11.1-17.5) in the control arm (n = 251; HR, 0.41; 95% CI, 0.31-0.53; P < .001). The 18-month PFS rates were 69% vs 43%, respectively.

The median OS was 33.9 months (95% CI, 21.9-NR) vs 15.2 months (95% CI, 12.3-21.1) in the investigational and control arms, respectively (HR, 0.57; 95% CI, 0.40-0.80). The 18-month OS rates were 84% vs 73%, respectively. The overall response rates were 83% (95% CI, 77%-87%) vs 71% (95% CI, 65%-77%), respectively. The respective median DOR was 35.6 months (95% CI, 30.5-NR) compared with 17.8 months (95% CI, 13.8-23.6).

In the safety population, all patients in the investigational arm (n = 242) and control arm (n = 246) experienced any-grade adverse effects (AEs). Grade 3 or higher AEs occurred at rates of 95% vs 78%, respectively. Patients in both arms experienced any-grade blood and lymphatic system disorders (76% vs 64%), infections and infestations (70% vs 67%), and ocular events (79% vs 29%). AEs leading to discontinuation of any study drug (5% vs 2%) and serious AEs leading to death (10% vs 8%) were also reported in both arms.

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://www.gsk.com/en-gb/media/press-releases/blenrep-shows-overall-survival-benefit-in-head-to-head-dreamm-7-phase-iii-trial-for-relapsedrefractory-multiple-myeloma/
2. 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