Exposure-response and dose simulation of belantamab mafodotin in combination with standards of care in patients with relapsed/refractory multiple myeloma

Le résumé fourni par la source

Belantamab mafodotin is approved globally for relapsed/refractory multiple myeloma (RRMM) based on the phase 3 DREAMM-7 (belantamab mafodotin, bortezomib, dexamethasone [BVd]) and DREAMM-8 (belantamab mafodotin, pomalidomide, dexamethasone) studies. Ocular events in these studies were common, transient, and associated with high rates of resolution. Exposure-response analyses using Cycle 1 exposures (data from the DREAMM-6, DREAMM-7, and DREAMM-8 trials) and BVd dosing regimen simulation (using a previously-developed and validated framework) were performed to support benefit-risk analysis of belantamab mafodotin dosing strategies to improve outcomes. Higher Cycle 1 belantamab mafodotin exposure was significantly associated with higher probabilities of overall response, very good partial response or better (≥VGPR), and shorter time to response, as well as ocular events including grade ≥2/≥3 ophthalmic exam findings (OEFs), and best-corrected visual acuity worsening to 20/50 or worse in both eyes. However, multivariate models predicted that the benefit of increased probability of ≥VGPR with a 2.5 mg/kg vs 1.9 mg/kg starting dose (70.4% vs 54.3%) outweighed the risk for modest increases in clinically meaningful ocular events. Simulated regimens with a 2.5 mg/kg first dose demonstrated high efficacy, with regimens that stepped down to 1.9 mg/kg and utilized schedule extensions (planned or in response to ocular events) showing improved tolerability. Altogether, a belantamab mafodotin starting dose of 2.5 mg/kg in RRMM is important to achieve deeper response and outweighs modest improvements in tolerability from a 1.9 mg/kg starting dose. Subsequent step-down to 1.9 mg/kg along with schedule extensions can be used to manage tolerability while still achieving meaningful efficacy.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.