Blenrep (belantamab mafodotin) combination reduced the risk of disease progression or death by nearly 50% versus standard of care combination in relapsed/refractory multiple myeloma

These late-breaking data, being presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (31 May – 4 June) in Chicago, IL, were featured in the official ASCO press programme and simultaneously published in the New England Journal of Medicine.

On the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.37-0.73], p-value<0.001) was observed with the belantamab mafodotin combination (n="155)" compared to the bortezomib combination (n="147)." at a median follow-up of 21.8 months, the median pfs was not yet reached (95% ci: 20.6-not yet reached [nr]) with the belantamab mafodotin combination compared to 12.7 months (95% ci: 9.1-18.5) in the bortezomib combination. at the end of one year, 71% (95% ci: 63-78) of patients in the belantamab mafodotin combination group compared to 51% (95% ci: 42-60) in the bortezomib combination group were alive and had not progressed. a benefit for belantamab mafodotin plus pomdex was observed across all pre-specified subgroups including those with poor prognostic features, such as patients who were refractory to lenalidomide and patients with high-risk cytogenetics.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse. This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators.”

A positive overall survival (OS) trend was observed but not statistically significant (HR: 0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further analyses are planned. At the end of one year, 83% (95% CI: 76-88) of patients were alive in the belantamab mafodotin combination group versus 76% (95% CI: 68-82) in the bortezomib combination group. The safety and tolerability profile of the belantamab mafodotin combination was broadly consistent with the known profile of the individual agents.

Suzanne Trudel, MD, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said: “The profound progression-free survival benefit seen in DREAMM-8 highlights the potential for belantamab mafodotin, when used with pomalidomide and dexamethasone, to improve outcomes for patients with relapsed/refractory multiple myeloma. This combination may have potential to redefine treatment of multiple myeloma at or after first relapse, a setting where patients may benefit from novel therapies.”

Similar to the results seen in the DREAMM-7 phase III head-to-head trial, in DREAMM-8 the belantamab mafodotin combination also resulted in clinically meaningful improvements consistently across secondary efficacy endpoints, showing that the belantamab mafodotin combination resulted in deeper and more durable responses compared to the bortezomib combination. Key improvements included rate of complete response (CR) or better (more than twofold improvement); minimal residual disease (MRD) negativity rate (nearly fivefold improvement); and duration of response (median not yet reached with the belantamab mafodotin combination versus 17.5 months with the bortezomib combination).

Grade 3 or higher non-ocular adverse events (AEs) of clinical interest in the belantamab mafodotin combination versus bortezomib combination arms, respectively, included neutropenia (57% versus 39%; 42 patients/100 personyears in both arms); thrombocytopenia (38% versus 29%; 28 vs 31 patients/100 person-years); and pneumonia (17% versus 8%; 13 versus 8 patients/100 person-years). Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally reversible, manageable with dose modifications, and led to low (9%) treatment discontinuation rates. Grade 3 or higher ocular adverse events occurred in 43% of patients receiving the belantamab mafodotin combination (Grade 3: 42%; Grade 4: 1%). Most commonly reported grade 3 or higher ocular symptoms included blurred vision (Grade 3: 17%; Grade 4: 0), dry eye (Grade 3: 8%: Grade 4: 0), and foreign body sensation in the eyes (Grade 3: 6%; Grade 4: 0). Fifty one patients (34%) with a best corrected visual acuity (BCVA) of 20/25 or better in at least one eye at baseline had a worsening in both eyes to 20/50 or worse. At the time of this analysis, the first occurrence of such events improved in 92% of these patients, and resolved in 85%, with a median time to resolution of 57 days (range: 14-451 days) .Global health status quality of life (QOL), as measured by the EORTC-QLQ-C30 remained stable in both treatment arms over time, suggesting that treatment did not lead to any decline in overall health related QOl .

See-" Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma "- Authors: Meletios Athanasios Dimopoulos, M.D., Meral Beksac, M.D., Ludek Pour, M.D.,+15, for the DREAMM-8 Investigators*s Published June 2, 2024 DOI: 10.1056/NEJMoa24034.