901P Matching-adjusted indirect comparisons (MAIC) of safety between single-agent belantamab mafodotin versus selinexor plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

Single-agent belantamab mafodotin (belamaf; GSK2857916), a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, demonstrated deep and durable responses in heavily pretreated patients with RRMM in DREAMM-2 (NCT03525678) primary and post hoc analyses. DREAMM-2 patients had ≥3 prior lines of therapy, were refractory to an immunomodulatory agent and a proteasome inhibitor, with anti-CD38 antibody exposure. Systematic searches for trials in a similar patient population to DREAMM-2 identified only STORM Part 2 (selinexor plus low-dose dexamethasone [sel+dex]; NCT02336815) for comparative analyses. MAIC were performed on populations receiving belamaf (2.5 mg/kg; n=97) versus sel+dex (sel 80 mg + dex 20 mg; n=123), matching for clinically validated effect modifiers and prognostic factors. Incidences of any grade and Grade 3–4 adverse events (AEs) among Grade 3–4 AEs affecting ≥5% of either trial population were compared. MAIC efficacy analyses are reported separately. Belamaf had lower risk (p<0.05) for frequent (≥25%) any-grade/Grade 3–4 thrombocytopenia, anaemia, neutropenia, fatigue, hyponatremia, and decreased appetite, and any-grade nausea and diarrhoea; (Table). Risk for any-grade/Grade 3–4 lymphopenia and hyperglycaemia, and any-grade leukopenia, pneumonia, hypokalaemia, and mental status changes was higher with belamaf than sel+dex. Keratopathy was reported in DREAMM-2 but not STORM Part 2. Hypercalcemia risk was higher with belamaf.Table: 901PMAIC of frequent (≥25%) AEsOR, 95% CIBelamaf 2.5 mg/kg vs sel+dexAny gradeGrade 3–4Thrombocytopenia*0.22 (0.12–0.43)‡0.20 (0.10–0.40)‡Anaemia0.15 (0.07–0.30)‡0.35 (0.17–0.72)‡Neutropenia0.07 (0.03–0.18)‡0.11 (0.03–0.34)‡Leukopenia0.27 (0.11–0.69)‡0.38 (0.09–1.61)Fatigue†0.07 (0.03–0.15)‡0.08 (0.02–0.36)‡Nausea0.10 (0.05–0.21)‡NEDiarrhoea0.15 (0.07–0.34)‡0.22 (0.03–1.83)Decreased appetite0.07 (0.03–0.17)‡NEHyponatremia0.06 (0.02–0.17)‡0.03 (0.01–0.16)‡OR <1 favours belamaf; OR <0.5, risk 50% lower with belamaf; NE, no Grade 3–4 event in DREAMM-2.*Includes thrombocytopenia, platelet count decreased; †Includes fatigue, asthenia; ‡p<0.05. Open table in a new tab OR <1 favours belamaf; OR <0.5, risk 50% lower with belamaf; NE, no Grade 3–4 event in DREAMM-2. *Includes thrombocytopenia, platelet count decreased; †Includes fatigue, asthenia; ‡p<0.05. MAIC of single-agent belamaf showed high efficacy and a favourable safety profile versus sel+dex for haematologic/non-haematologic AEs reported in compared studies.