Belantamab mafodotin is a first-in-class, B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate that has shown promising antitumor activity in RRMM, particularly when combined with immunomodulatory agents. Pomalidomide and dexamethasone (Pd) represent a widely used backbone in RRMM, and the addition of novel agents to this doublet is a key strategy to deepen responses and delay disease progression after lenalidomide exposure. The DREAMM-8 trial (NCT04484623) was designed to evaluate the efficacy and safety of combining belantamab mafodotin with Pd (BPd) compared to the established triplet regimen of PVd in RRMM patients who had received at least one prior line of therapy, including lenalidomide. Previous analyses demonstrated a statistically significant progression-free survival (PFS) benefit with BPd (HR, 0.52), prompting further investigation with longer follow-up.

With a median follow-up of 28 months, updated results from DREAMM-8 confirm and extend the initial findings. The BPd regimen significantly prolonged median PFS to 32.6 months vs. 12.5 months with PVd, with a notably higher 18-month PFS rate (63% vs. 41%). Importantly, the benefit of BPd was maintained across key high-risk subgroups, including those with high-risk cytogenetics, lenalidomide-refractory disease, and both early (1 prior LOT) and more heavily pretreated patients (≥2 prior LOTs). The favorable efficacy signal was not accompanied by new safety concerns; the toxicity profile remained consistent with prior reports. These data support BPd as a potent and durable option in the first relapse setting, potentially offering a new standard for RRMM patients, particularly those with limited options after lenalidomide exposure.

KOL insights

“Overall, in combination with the significant progression-free survival benefit generated with BPd vs PVd, as observed in DREAMM-8, these results further support the use of BPd as a potential new standard of care in patients with relapsed/refractory multiple myeloma,”– Expert Opinion

Conclusion

There are many types of drugs that can treat multiple myeloma, a cancer of plasma cells. Some of these drugs work by themselves or with others, such as: drugs that affect the immune system (IMIDs), like REVLIMID and POMALYST; drugs that target a protein called CD38 on the surface of multiple myeloma cells, like DARZALEX and SARCLISA; drugs that bind to another protein called SLAM7, like EMPLICITI; and drugs that block the activity of enzymes called proteasomes, like VELCADE, KYPROLIS, and NINLARO. These drugs have improved the survival of multiple myeloma patients in the last 10 years, but most of them will still have their disease come back after the first treatment. 

BLENREP is the sole anti-BCMA antibody-drug conjugate (ADC) available for multiple myeloma, offering a distinct mechanism of action for patients at or following relapse. Its combination regimens are suitable for diverse patient populations and can be delivered across various oncology care settings without the need for complicated pre-treatment protocols or hospitalization. In November 2022, GSK requested withdrawal of the biologics license for BLENREP powder for injection and waived its opportunity for a hearing. Later in February 2024, the European Commission (EC) implemented its decision not to renew the conditional marketing authorization for BLENREP. Recently in April 2025, BLENREP is approved for the treatment of adults with multiple myeloma in combination with bortezomib plus dexamethasone (BVd) in patients who have received at least one prior therapy, and in combination with pomalidomide plus dexamethasone (BPd) in patients who have received at least one prior therapy including lenalidomide. Additional T-cell–redirecting therapies targeting BCMA are expected to become available, making it increasingly important to consider disease- and patient-specific factors when determining the most suitable treatment option.