Abstract 901P
Background
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.
Methods
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.
Results
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: 901P
MAIC of frequent (≥25%) AEs
| OR, 95% CI | Belamaf 2.5 mg/kg vs sel+dex | |
| Any grade | Grade 3–4 | |
| Thrombocytopenia* | 0.22 (0.12–0.43)‡ | 0.20 (0.10–0.40)‡ |
| Anaemia | 0.15 (0.07–0.30)‡ | 0.35 (0.17–0.72)‡ |
| Neutropenia | 0.07 (0.03–0.18)‡ | 0.11 (0.03–0.34)‡ |
| Leukopenia | 0.27 (0.11–0.69)‡ | 0.38 (0.09–1.61) |
| Fatigue† | 0.07 (0.03–0.15)‡ | 0.08 (0.02–0.36)‡ |
| Nausea | 0.10 (0.05–0.21)‡ | NE |
| Diarrhoea | 0.15 (0.07–0.34)‡ | 0.22 (0.03–1.83) |
| Decreased appetite | 0.07 (0.03–0.17)‡ | NE |
| Hyponatremia | 0.06 (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.
Conclusions
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.
Clinical trial identification
DREAMM-2: NCT03525678; STORM: NCT02336815.
Editorial acknowledgement
Editorial assistance was provided by Muchaala Yeboah, PhD, of Fishawack Indicia Ltd and funded by GlaxoSmithKline.
Legal entity responsible for the study
Study funded by GlaxoSmithKline.
Funding
Study funded by GlaxoSmithKline 207147. Drug linker technology licensed from Seattle Genetics; Monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Disclosure
A. Suvannasankha: Advisory/Consultancy: GlaxoSmithKline, Janssen, and Karyopharm Therapeutics; Research grant/Funding (self): GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and Celgene; Travel/Accommodation/Expenses: GlaxoSmithKline and Janssen. T. Prawitz, V. Kapetanakis, G. Sarri, R. Hughes, F. Wang, C. Hogea, S. Allen Ferrante, B. Gutierrez, B. Gorsh, J. Willson: Research grant/Funding (self): employee of Evidera which received research funding from GlaxoSmithKline. R. Popat: Honoraria (self), Honoraria (institution): Janssen, Takeda, Celgene, and GlaxoSmithKline; Advisory/Consultancy: Takeda, AbbVie, GlaxoSmithKline, and Celgene; Research grant/Funding (self): Takeda; Travel/Accommodation/Expenses: Janssen, Takeda, and GlaxoSmithKline.