The use of triplet and quadruplet therapies in first-line treatment for multiple myeloma creates a need for new combinations at first relapse, which BLENREP (belantamab mafodotin; belamaf) combinations may address. In the DREAMM-7 study, BLENREP combined with bortezomib and dexamethasone (BVd) significantly improved progression-free survival (PFS) and showed a strong trend towards improved overall survival (OS) compared to daratumumab-Vd in patients with at least one prior therapy. 

In EHA 2024 GSK presented results from DREAMM-8 (NCT04484623), which tested a different combination of BLENREP with pomalidomide and dexamethasone (BPd), meeting its primary endpoint of independent review committee–assessed progression-free survival (PFS) at a prespecified interim analysis.

In the DREAMM-8 study, 155 patients were randomly assigned to the BPd group and 147 to the PVd group. With a median follow-up of 21.8 months, the median progression-free survival (PFS) was not reached (20.6–NR) for BPd, compared to 12.7 months (9.1–18.5) for PVd (HR: 0.52; 95% CI: 0.37–0.73; p < 0.001).

The 12-month PFS rate was 71% for BPd versus 51% (95% CI: 42–60%) for PVd. The overall response rate (ORR) was 77% (95% CI: 70.0-83.7%) for BPd compared to 72% (95% CI: 64.1–79.2%) for PVd. The rate of complete response or better was 40% (95% CI: 32.2-48.2%) for BPd versus 16% (95% CI: 10.7-23.3%) for PVd. The median duration of response was not reached (95% CI: 24.9-NR) for BPd compared to 17.5 months (95% CI: 12.1-26.4) for PVd. 

A positive trend favoring BPd was observed for OS (HR: 0.77; 95% CI: 0.53-1.14), with follow-up ongoing. 

Adverse events (AEs) were reported in over 99% of patients in the BPd arm and 96% in the PVd arm. In the BPd group, 89% experienced ocular AEs (43% grade 3/4) compared to 30% (2% grade 3/4) in the PVd group. AEs were generally manageable and consistent with the known safety profiles of the individual agents. So far, the results align with the findings of the DREAMM-7 study, which compared BENREP to Darzalex added to Takeda’s bortezomib and dexamethasone as a second-line treatment. That study demonstrated a 59% reduction in PFS risk and a 43% trend towards improved OS.

KOL insights

“Belantamab mafodotin in combination with BorDex could offer the potential for a BCMA-targeted treatment option with wide patient eligibility and an in-office infusion process in a community oncology treatment center, potentially improving the patient experience.” – MD, United States

Conclusion 

BLENREP was initially granted accelerated and conditional marketing authorization in the US and EU based on results from the DREAMM-2 trial, in the fourth line and above. However, the subsequent Phase III DREAMM-3 trial in the third-line and above setting did not achieve its primary endpoint of PFS, leading to the withdrawal from the US market. Then the European Medicines Agency (EMA) also decided to revoke the conditional marketing authorization starting in 2024. 

GSK aims to advance BLENREP into earlier-line therapy based on the DREAMM-7 and DREAMM-8 data and is eager to discuss the results with regulators. GSK believes that the drug could "redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care." Positive results from the DREAMM-8 and DREAMM-7 trials could mark BLENREP’s potential return as a promising treatment for relapsed refractory multiple myeloma. 

Multiple Myeloma is crowded and BLENREP has to compete with BCMA-directed CAR-T cell therapies along with BCMA-directed bispecific antibodies. Two CAR-T therapies—Bristol-Myers Squibb’s ABECMA and Johnson & Johnson’s CARVYKTI are now approved for later-line use in multiple myeloma, along with two BCMA x CD3 bispecific antibodies, J&J’s TECVAYLI and Pfizer’s ELREXFIO. It is worth noting that CARVYKTI has become the first FDA approved BCMA-directed therapy for multiple myeloma patients who have received at least just one prior line of therapy.