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Clinical Trial
. 2025 Sep;20(5):833-845.
doi: 10.1007/s11523-025-01174-0. Epub 2025 Sep 16.

"VSports" Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study

Patrick Hanafin  1 , Yu Liu Ho  1 , Theodoros Papathanasiou  2 , Giulia Fulci  3 , Neal Sule  1 , Brandon E Kremer  1 , Geraldine Ferron-Brady  4
Affiliations
Clinical Trial

Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study

"V体育官网入口" Patrick Hanafin et al. Target Oncol. 2025 Sep.

Abstract

Background: 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). VSports手机版.

Objective: 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 V体育安卓版. 5 mg/kg using DREAMM-8 data. .

Patients and methods: In the BPd arm of DREAMM-8, belantamab mafodotin was dosed at 2 V体育ios版. 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. .

Results: 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 VSports最新版本. 5 mg/kg would result in reduction in probability of ≥ CR without reduction in oAEs/ophthalmic exam findings. .

Conclusions: 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 V体育平台登录. gov (21 July 2020). .

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Conflict of interest statement

Declarations. Funding: Study 207499 and the analyses reported herein were funded by GSK. Drug linker technology licensed from Seagen Inc. ; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Conflicts of Interest: P. Hanafin, Y. L. Ho, T. Papathanasiou, G. Fulci, N. Sule, B. E. Kremer, and G. Ferron-Brady are employees of and hold financial equities in GSK. Ethics Approval: The DREAMM-8 trial protocol and amendments were approved by the appropriate ethics body at each participating institution VSports注册入口. Consent to Participate: All patients provided written informed consent before enrollment in DREAMM-8. Consent for Publication: N/A Data Availability: GSK makes available anonymized individual participant data and associated documents from interventional clinical studies that evaluate medicines, upon approval of proposals submitted to https://www. gsk-studyregister. com/en/ . Code Availability: N/A. Author Contributions: Conceptualization and design: P. Hanafin, Y. L. Ho, T. Papathanasiou, G. Fulci, N. Sule, B. E. Kremer, and G. Ferron-Brady; Data collection and analysis: P. Hanafin, Y. L. Ho, T. Papathanasiou, G. Fulci, N. Sule, B. E. Kremer, and G. Ferron-Brady; Writing—review and editing: P. Hanafin, Y. L. Ho, T. Papathanasiou, G. Fulci, N. Sule, B. E. Kremer, and G. Ferron-Brady. The first draft of the manuscript was written by Alexus Rivas-John and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Figures

Fig. 1
Fig. 1
Progression-free survival stratified by cycle 1 belantamab mafodotin Cavg quartile (a) and baseline sBCMA quartile (b). Duration of response stratified by cycle 1 belantamab mafodotin Cavg quartile (c) and baseline sBCMA quartile (d). Quartiles are reported as median (minimum, maximum). ADC antibody-drug conjugate, sBCMA soluble B-cell maturation antigen, Cavg average concentration over the dosing interval, Q quartile
Fig. 2
Fig. 2
Relationship between probabilities of clinical response and cycle 1 belantamab mafodotin Cavg. The independent variable was divided into quartiles. Quartiles are reported as median (minimum, maximum). Points and error bars represent the observed proportions and 95% confidence intervals for each quartile (plotted at the median exposure within each quartile), respectively. The curves represent the prediction of the univariate logistic regression model, and the shaded region represents the 95% confidence interval of the prediction. The displayed p-value is for the logistic regression slope. ADC, antibody-drug conjugate; Cavg, average concentration over the dosing interval; ≥ CR, complete response or better; MRD, minimal residual disease; ≥ OR, overall response or better; Q, quartile; ≥ VGPR, very good partial response or better
Fig. 3.
Fig. 3.
Time to response stratified by cycle 1 belantamab mafodotin Cavg quartile. Quartiles are reported as median (minimum, maximum). ADC antibody-drug conjugate, Cavg average concentration over the dosing interval, Q quartile
Fig. 4.
Fig. 4.
Relationship between probability of ≥ VGPR, oAEs, OEFs, and cycle 1 belantamab mafodotin Cavg. The independent variable was divided into quartiles. Quartiles are reported as median (minimum, maximum). Points and error bars represent the observed proportions and 95% confidence intervals for each quartile (plotted at the median exposure within each quartile), respectively. The curves represent the prediction of the univariate logistic regression model, and the shaded region represents the 95% confidence interval of the prediction. The displayed p-value is for the logistic regression slope. ADC antibody-drug conjugate, BCVA best corrected visual acuity, Cavg average concentration over the dosing interval, KVA keratopathy and visual acuity, oAE ocular adverse event, OEF ophthalmic exam finding, Q quartile; ≥ VGPR very good partial response or better
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References (V体育2025版)

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