MM-209: Assessing Efficacy via Indirect Comparison of Single-Agent Belantamab Mafodotin (Belamaf; GSK2857916) in DREAMM-2 Versus STORM or MAMMOTH Studies in Relapsed/Refractory Multiple Myeloma (RRMM)

Abstract

Context: Patients with RRMM who have progressed following standard-of-care (SoC) regimens have limited treatment options. Single-agent belamaf demonstrated deep and durable responses in heavily pretreated patients with RRMM in the DREAMM-2 primary analysis (NCT03525678; Lonial et al. Lancet Oncol 2020). Objective: To indirectly compare the efficacy of single-agent belamaf versus appropriate comparators in similar patient populations (received ≥3 prior lines of treatment, refractory to anti-CD38 therapies) in a post-hoc analysis of DREAMM-2. Methods: Following a systematic literature review, STORM Part 2 (NCT02336815) study of selinexor+dexamethasone (sel+dex) was identified as a feasible comparator. Matching-adjusted indirect comparisons (MAIC) were performed to investigate the efficacy of single-agent belamaf (DREAMM-2) versus sel+dex (STORM) by matching populations for all available, clinically-validated effect modifiers, and prognostic factors (Popat et al ASCO 2020 e10527; EHA 2020 EP1016). Belamaf efficacy vs SoC was estimated by Bucher indirect treatment comparison (ITC) of MAIC results with the relative efficacy of sel+dex versus SoC in a patient subset# from MAMMOTH (retrospective, natural history study of patients with RRMM following SoC), evaluated against a comparable STORM subset (Costa et al. Blood 2019). Results: MAIC and Bucher ITC analyses suggested significantly longer overall survival (OS) with single-agent belamaf versus sel+dex (hazard ratio [HR] [95% CI]: 0.60 [0.39–0.94]; p=0.025) and SoC (HR [95% CI]: 0.33 [0.17–0.63]; p < 0.001). MAIC results suggested significantly longer duration of response (DoR) for belamaf (HR [95% CI]: 0.34 [0.13–0.90]; p=0.030) compared with sel+dex. Overall response rates (odds ratio [97.5% CI]: 0.95 [0.5–1.83]; p=0.88), time to response (HR [95% CI]: 0.76 [0.46–1.23]; p=0.26), and progression-free survival (HR [95% CI]: 1.34 [0.89–2.00]; p=0.16) were not statistically different. Conclusions: MAIC indicated significant improvements in OS and DoR with single-agent belamaf versus sel+dex in heavily pretreated RRMM patients. Subject to the shared treatment effect modifiers assumption, Bucher ITC suggested significantly improved OS with belamaf versus SoC. Additional analyses will inform safety comparisons. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. #Penta-exposed (bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab); refractory to ≥one proteasome inhibitor, one immunomodulatory agent, and daratumumab. Patients with RRMM who have progressed following standard-of-care (SoC) regimens have limited treatment options. Single-agent belamaf demonstrated deep and durable responses in heavily pretreated patients with RRMM in the DREAMM-2 primary analysis (NCT03525678; Lonial et al. Lancet Oncol 2020). To indirectly compare the efficacy of single-agent belamaf versus appropriate comparators in similar patient populations (received ≥3 prior lines of treatment, refractory to anti-CD38 therapies) in a post-hoc analysis of DREAMM-2. Following a systematic literature review, STORM Part 2 (NCT02336815) study of selinexor+dexamethasone (sel+dex) was identified as a feasible comparator. Matching-adjusted indirect comparisons (MAIC) were performed to investigate the efficacy of single-agent belamaf (DREAMM-2) versus sel+dex (STORM) by matching populations for all available, clinically-validated effect modifiers, and prognostic factors (Popat et al ASCO 2020 e10527; EHA 2020 EP1016). Belamaf efficacy vs SoC was estimated by Bucher indirect treatment comparison (ITC) of MAIC results with the relative efficacy of sel+dex versus SoC in a patient subset# from MAMMOTH (retrospective, natural history study of patients with RRMM following SoC), evaluated against a comparable STORM subset (Costa et al. Blood 2019). MAIC and Bucher ITC analyses suggested significantly longer overall survival (OS) with single-agent belamaf versus sel+dex (hazard ratio [HR] [95% CI]: 0.60 [0.39–0.94]; p=0.025) and SoC (HR [95% CI]: 0.33 [0.17–0.63]; p < 0.001). MAIC results suggested significantly longer duration of response (DoR) for belamaf (HR [95% CI]: 0.34 [0.13–0.90]; p=0.030) compared with sel+dex. Overall response rates (odds ratio [97.5% CI]: 0.95 [0.5–1.83]; p=0.88), time to response (HR [95% CI]: 0.76 [0.46–1.23]; p=0.26), and progression-free survival (HR [95% CI]: 1.34 [0.89–2.00]; p=0.16) were not statistically different. MAIC indicated significant improvements in OS and DoR with single-agent belamaf versus sel+dex in heavily pretreated RRMM patients. Subject to the shared treatment effect modifiers assumption, Bucher ITC suggested significantly improved OS with belamaf versus SoC. Additional analyses will inform safety comparisons.