▎Edited by the WuXi AppTec content team

Recently, GSK announced the interim analysis results of the Phase 3 clinical trial DREAMM-7. This trial compared and evaluated the efficacy of Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone (BorDex) versus the current standard treatment regimen (daratumumab plus BorDex) for relapsed or refractory multiple myeloma in second-line and later treatments. The results showedCompared with the standard combination therapy, the median progression-free survival (PFS) of Blenrep combination therapy has increased nearly twice.。

In terms of PFS, the primary endpoint, belantamab mafodotin combination therapy (n=243) demonstrated statistically significant and clinically meaningful improvement compared to the standard treatment regimen (n=251).The risk of disease progression or death was reduced by 59% ([HR]: 0.41, [95% CI: 0.31-0.53], P<0.00001). The median follow-up time was 28.2 months, with a median PFS of 36.6 months (95% CI: 28.4-not yet reached [NR]) for the belantamab mafodotin combination therapy, compared to a median PFS of 13.4 months (11.1-17.5 months) for the daratumumab combination therapy.An impact on PFS was observed across all predefined subgroups, including lenalidomide-refractory patients and those with high-risk cytogenetic features. The safety and tolerability of the belantamab mafodotin combination regimen were consistent with the known profile of the monotherapy.

Belantamab mafodotin combination therapy also led to clinically meaningful improvements in all secondary efficacy endpoints, including doubling the rates of complete response (stringent complete response + complete response), minimal residual disease (MRD) negativity, and median duration of response (DOR).。In the interim analysis, the researchers observed a strong and clinically meaningful trend in overall survival (OS), with a 43% reduction in the risk of death (HR: 0.57, [95% CI: 0.40-0.80], P=0.00049), but the interim criteria for statistical significance in OS have not yet been met. Follow-up for OS is ongoing, and the researchers plan to conduct further analyses.

Belantamab mafodotin is an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA)., composed of a humanized anti-BCMA monoclonal antibody and the cytotoxic drug auristatin F (auristatin F) conjugated through a non-cleavable linker, which can eliminate myeloma cells through multiple mechanisms of action.. The drug received Breakthrough Therapy Designation from the U.S. FDA in 2017 and was approved by the FDA in August 2020.Accelerated Approval`, becoming the world's first approved therapy targeting BCMA.`

In the belantamab mafodotin combination therapy group and the daratumumab combination therapy group, clinically notable Grade 3 or higher non-ocular adverse events included thrombocytopenia (55% and 35%, respectively; adjusted incidence rates of 40 cases/100 person-years and 29 cases/100 person-years, respectively), neutropenia (12% and 6%), pneumonia (12% and 4%; adjusted incidence rates of 8 cases/100 person-years and 3 cases/100 person-years, respectively), and anemia (8% and 10%).

Image Source: 123RF

The side effects of Belantamab mafodotin treatment are mainly related to ocular adverse reactions, which is one of the known risks of this drug treatment. However, these side effects are usually reversible and can be controlled by adjusting the dosage.The proportion of treatment discontinuations due to eye-related side effects was low (9%).34% of patients receiving belantamab mafodotin combination therapy experienced grade 3 or higher ocular adverse reactions, mainly including blurred vision (22%), dry eye (7%), eye irritation (5%), and visual impairment (5%). Among 82 patients (34%) who had a best-corrected visual acuity (BCVA) of 20/25 or better in at least one eye at baseline, both eyes deteriorated to 20/50 or worse. At the time of analysis, nearly all of these patients (98%) had resolution of their adverse reactions. The median time to resolution of adverse reactions was 22 days.

According to the overall health status quality of life (QOL) assessed by the EORTC-QLQ-C30 scale, there was no difference in the overall QOL among different treatment groups over time.

The DREAMM clinical development program will continue to evaluate the potential of belantamab mafodotin in earlier lines of treatment for multiple myeloma, as well as its potential in combination with novel and standard therapies. This includes the ongoing Phase III DREAMM-8 trial, which compares the combination therapy of belantamab mafodotin with pomalidomide and dexamethasone to the regimen of bortezomib with pomalidomide and dexamethasone. Data from the DREAMM-8 trial are expected to be announced in the second half of 2024.

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