MM-250: Impact of Prolonged Dose Delays on Response with Belantamab Mafodotin (Belamaf; GSK2857916) Treatment in the DREAMM-2 Study: 13-Month Follow-Up

CONTEXT: Single-agent belamaf demonstrated deep and durable responses in the DREAMM-2 (NCT03525678) primary analysis (1) and long-term follow-up (2,3). Keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination with/without symptoms) were managed through dose delays and reductions. OBJECTIVE: To provide an update on the impact of dose delays on responses in patients receiving single-agent belamaf 2.5-mg/kg in DREAMM-2 (13-month follow-up). METHODS: In the DREAMM-2 study (single-agent belamaf 2.5 mg/kg [n=97] or 3.4 mg/kg [n=99] Q3W), dose modifications were permitted to manage adverse events (AEs), including keratopathy (MECs), an eye examination finding that may/may not be associated with symptoms. Objective response (IMWG criteria 2016) was assessed by an independent review committee Q3W, regardless of treatment delays. Here, we report a post-hoc analysis on the impact of dose delays >63 days on clinical response in the 2.5-mg/kg arm (the selected dose for future clinical development based on risk–benefit assessment). RESULTS: In patients receiving single-agent belamaf (2.5 mg/kg), dose delays (54%) and reductions (35%) due to AEs were common (2,3). Keratopathy (MECs) was the most frequent reason for dose delays (47%) and reductions (25%), leading to only 1 patient (1%) discontinuing treatment (2,3). Of 31 patients with ≥partial response, 16 had prolonged treatment interruptions (>63 days). Of these 16 patients, 14 (88%) continued experiencing a clinical benefit during the first prolonged delay: 6 (38%) deepened their response during delay (1 SD to MR; 2 PR to VGPR; 2 MR to VGPR; 1 VGPR to CR); 6 (38%) maintained the same response category as that of the last evaluable assessment during delay/first evaluable assessment after delay; 2 (13%) had increasing paraproteins during the delay but did not meet progression criteria. Two (13%) developed disease progression (1 patient 6 weeks into delay; 1 patient 3 weeks after delay). CONCLUSIONS: Despite dose delays lasting for several cycles to manage AEs, most responses were sustained throughout the delay, thus maintaining clinical benefit for the majority of patients. FUNDING: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. REFERENCES: [1] Lonial Lancet Oncol 2020. [2] Lonial ASCO 2020, EP436. [3] Lonial EHA 2020, EP970.