Belantamab Mafodotin Plus Proteasome Inhibition Efficacy Versus Comparators in Early Relapsed Myeloma: A Systematic Review and Network Meta‐Analysis

ABSTRACT In the Phase 3 DREAMM‐7 study of patients with relapsed/refractory multiple myeloma (RRMM) who received ≥ 1 prior therapy, belantamab mafodotin plus bortezomib and dexamethasone (BVd) demonstrated a progression‐free survival (PFS) benefit versus daratumumab plus bortezomib and dexamethasone (DVd). This study aimed to indirectly compare the efficacy of BVd against alternative regimens in this patient population. A systematic literature review (SLR; December 2021–February 4, 2024) was performed to identify relevant efficacy data. Studies were selected based on the Population‐Intervention‐Comparators‐Outcomes‐Study design framework criteria and independently reviewed for inclusion in the network meta‐analysis (NMA) if they had a connection to DREAMM‐7 (approved in the US or EU, or likely to be a future DREAMM‐7 comparator). Each trial had a common comparator arm, allowing for a connected network between the trials and linkage by shared treatments. The primary analysis was PFS in the intent‐to‐treat population from each study, and secondary analyses examined other endpoints. All endpoints were also evaluated in subgroups by lenalidomide‐exposure, ‐refractoriness, and other patient characteristics. The SLR identified 12 comparator studies comprising 12 comparator regimens (each contained a proteasome inhibitor [bortezomib or carfilzomib] plus dexamethasone), all of which were included in the NMA with the DREAMM‐7 study. BVd improved PFS versus all comparators, including daratumumab plus carfilzomib and dexamethasone, isatuximab plus carfilzomib and dexamethasone, and DVd. Overall survival was also improved by belantamab mafodotin plus bortezomib and dexamethasone over the other regimens. This study provides compelling evidence for belantamab mafodotin, plus bortezomib and dexamethasone, in early lines of treatment for RRMM.