Hanafin Patrick, Ho Yu Liu, Papathanasiou Theodoros, Fulci Giulia, Sule Neal, Kremer Brandon E, Ferron-Brady Geraldine
GSK, 1250 S Collegeville Rd, Collegeville, PA, 19426, USA.
GSK, Baar, Switzerland.
Target Oncol. 2025 Sep 16. doi: 10.1007/s11523-025-01174-0.
In the phase 3 DREAMM-8 study (NCT04484623), belantamab mafodotin (anti-B-cell maturation antigen [BCMA] antibody-drug conjugate with a monomethyl auristatin F payload) with pomalidomide and dexamethasone (BPd) showed significant progression-free survival benefit in second-line or later relapsed/refractory multiple myeloma (RRMM).
This exposure-response analysis explored the relationship between belantamab mafodotin cycle 1 exposure and efficacy/safety and predicted the benefit-risk profile of belantamab mafodotin at an initial dose of 1.9 versus 2.5 mg/kg using DREAMM-8 data.
In the BPd arm of DREAMM-8, belantamab mafodotin was dosed at 2.5 mg/kg intravenously in cycle 1, then at 1.9 mg/kg every 4 weeks from cycle 2 onward. Cycle 1 belantamab mafodotin and free payload exposures derived from population pharmacokinetic analysis were used to perform exposure-efficacy/exposure-safety analyses for probability of/time to first event. Selected covariate effects were evaluated.
Higher belantamab mafodotin cycle 1 exposure was associated with deeper response (higher probabilities of complete response or better [≥ CR] and minimal residual disease negativity), but not with grade ≥ 3 ocular adverse events (oAEs)/ophthalmic exam findings. Benefit-risk assessment showed that an initial belantamab mafodotin dose of 1.9 mg/kg instead of 2.5 mg/kg would result in reduction in probability of ≥ CR without reduction in oAEs/ophthalmic exam findings.
An initial belantamab mafodotin dose of 2.5 mg/kg for BPd yields deeper responses versus 1.9 mg/kg with minimal change in safety outcomes in RRMM. DREAMM-8 (NCT04484623) was registered at clinicaltrials.gov (21 July 2020).
在3期DREAMM - 8研究（NCT04484623）中，贝兰他单抗莫福汀（一种与单甲基奥瑞他汀F有效载荷结合的抗B细胞成熟抗原[BCMA]抗体药物偶联物）联合泊马度胺和地塞米松（BPd）在二线或更晚期复发/难治性多发性骨髓瘤（RRMM）中显示出显著的无进展生存获益。
这项暴露 - 反应分析探讨了贝兰他单抗莫福汀第1周期暴露与疗效/安全性之间的关系，并使用DREAMM - 8数据预测了初始剂量为1.9 mg/kg与2.5 mg/kg时贝兰他单抗莫福汀的获益 - 风险概况。
在DREAMM - 8的BPd治疗组中，贝兰他单抗莫福汀在第1周期静脉注射剂量为2.5 mg/kg，从第2周期起每4周剂量为1.9 mg/kg。通过群体药代动力学分析得出的第1周期贝兰他单抗莫福汀和游离有效载荷暴露量用于进行首次事件发生概率/时间的暴露 - 疗效/暴露 - 安全性分析。评估了选定协变量的影响。
较高的贝兰他单抗莫福汀第1周期暴露与更深的缓解相关（完全缓解或更好[≥CR]以及微小残留病阴性的概率更高），但与≥3级眼部不良事件（oAE）/眼科检查结果无关。获益 - 风险评估表明，初始贝兰他单抗莫福汀剂量为1.9 mg/kg而非2.5 mg/kg会导致≥CR概率降低，而oAE/眼科检查结果无降低。
对于RRMM，BPd方案中贝兰他单抗莫福汀初始剂量为2.5 mg/kg比1.9 mg/kg产生更深的缓解，且安全性结果变化最小。DREAMM - 8（NCT04484623）于2020年7月21日在clinicaltrials.gov注册。
