Belantamab Mafodotin Combo Halves Disease Progression Risk in Relapsed/Refractory Multiple Myeloma

GSK plc has announced promising interim results from its DREAMM-8 phase III clinical trial, which evaluates belantamab mafodotin in combination with pomalidomide and dexamethasone (PomDex) against a standard therapy of bortezomib plus PomDex for treating relapsed or refractory multiple myeloma. These findings were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine.

The study primarily focused on progression-free survival (PFS), revealing a statistically significant and clinically meaningful improvement with the belantamab mafodotin combination. Specifically, the hazard ratio (HR) was 0.52, indicating a 48% reduction in the risk of disease progression or death compared to the bortezomib combination. At a median follow-up of 21.8 months, the median PFS for the belantamab mafodotin group had not yet been reached, in contrast to 12.7 months for the bortezomib group. After one year, 71% of patients in the belantamab mafodotin combination group were alive without disease progression compared to 51% in the bortezomib combination group.

The benefits observed with the belantamab mafodotin combination were consistent across various subgroups, including patients with poor prognostic features such as lenalidomide-refractory disease and high-risk cytogenetics. The overall survival (OS) trend was also positive, though not statistically significant at the interim analysis, with 83% of patients in the belantamab mafodotin group alive at the one-year mark compared to 76% in the bortezomib group.

Dr. Hesham Abdullah, GSK's Senior Vice President, Global Head Oncology, R&D, highlighted the significance of these results, noting that this is the second phase III trial to demonstrate the efficacy of a belantamab mafodotin combination in treating multiple myeloma. Dr. Suzanne Trudel from Princess Margaret Cancer Centre emphasized the profound PFS benefits and the potential of this combination to improve outcomes for patients with relapsed or refractory multiple myeloma.

Compared to the bortezomib combination, the belantamab mafodotin combination showed improvements across several secondary efficacy endpoints. These included a more than twofold increase in the rate of complete response (CR), a nearly fivefold improvement in minimal residual disease (MRD) negativity rate, and a longer duration of response, which was not reached in the belantamab mafodotin group but was 17.5 months in the bortezomib group.

The overall response rate (ORR) was higher in the belantamab mafodotin combination group at 77% compared to 72% in the bortezomib combination group. The rate of stringent complete response (sCR) and very good partial response (VGPR) was also higher in the belantamab mafodotin group.

Regarding safety and tolerability, the profile of the belantamab mafodotin combination was generally consistent with known effects from individual agents. Grade 3 or higher non-ocular adverse events included neutropenia, thrombocytopenia, and pneumonia. Eye-related side effects, a known risk with belantamab mafodotin, were manageable and led to low treatment discontinuation rates. Most ocular adverse events were reversible, and vision impairment events improved significantly over time.

Quality of life, measured by the EORTC-QLQ-C30, remained stable in both treatment groups, indicating that the treatment did not adversely affect overall health-related quality of life.

The DREAMM-8 trial involved 302 patients who had previously undergone at least one line of multiple myeloma therapy, including a lenalidomide-containing regimen. The study's primary endpoint was PFS, with secondary endpoints including OS, MRD negativity, duration of response, overall response rate, patient-reported quality of life outcomes, adverse events, and laboratory findings.

In conclusion, the DREAMM-8 phase III trial results suggest that the belantamab mafodotin combination could potentially redefine the treatment landscape for relapsed or refractory multiple myeloma, offering significant improvements in progression-free survival and overall response rates.