Safety and clinical activity of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-6 arm-A interim analysis.

Abstract

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Background: Belantamab mafodotin (belamaf; BLENREP) is a B-cell maturation antigen-targeting antibody–drug conjugate approved for patients (pts) with RRMM as monotherapy at 2.5 mg/kg Q3W. Preclinical data demonstrate synergy between belamaf and lenalidomide (Len), suggesting added benefit when combined with standard of care such as Len + dexamethasone (Dex). DREAMM-6 (NCT03544281) Arm A is evaluating belamaf in combination with LenDex in pts with RRMM. Methods: This ongoing, two-part, two-arm, open-label study included pts with RMMM previously treated with ≥1 line of therapy (LOT). Pts received 4 belamaf doses/schedules (1.9 mg/kg Q8W or Q4W; 2.5 mg/kg Q4W or Q4W SPLIT dose [50% on Days (D)1, 8] IV) in combination with Len (20 mg PO D1–21) and Dex (20 mg PO/IV D1, 8, 15, 22). Primary objectives were safety (including treatment-related [TR]AEs related to the combination belamaf and LenDex), tolerability, and efficacy (including overall response rate [ORR] defined as ≥partial response). Results: As of this interim analysis (data cut: July 23, 2021), 45 pts received ≥1 dose (12 at 1.9 mg/kg Q8W; 4 at 1.9 mg/kg Q4W; 16 at 2.5 mg/kg Q4W; 13 at 2.5 mg/kg Q4W SPLIT). Across cohorts, the median age was 68 y (range: 36–80). Thirteen pts (29%) had high-risk cytogenetics and 6 (13%) had extramedullary disease. Median prior LOT was 3 (range: 1–11) and 26 (58%) had prior Len treatment. The median duration of follow-up and ORR ranged across cohorts (Table). The median duration of response was only reached in the 1.9 mg/kg Q4W cohort (11.1 mo [95% CI: 3.7–not reached [NR]). At the time of data cut, median progression-free survival was not reached in the 1.9 mg/kg Q8W or 2.5 mg/kg Q4W cohorts. Gr ≥3 TRAEs occurred in 42–85%. Gr ≥3 keratopathy occurred in 0 pts in 1.9 mg/kg Q8W, 1 pt (25%) in 1.9 mg/kg Q4W, 8 pts (50%) in 2.5 mg/kg Q4W, and 6 pts (46%) in 2.5 mg/kg Q4W SPLIT cohorts. Conclusions: Belamaf + LenDex had a tolerable safety profile, with no new safety signals identified in pts with RRMM. AEs, including keratopathy, were common but manageable with dose modifications. Encouraging clinical activity is observed with this combination in pts with RRMM. Follow-up/correlative studies are ongoing. Funding: GSK (Study 207497); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281. [Table: see text]