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

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).

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 2.5 mg/kg using DREAMM-8 data.

Patients and methods: 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.

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 2.5 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.gov (21 July 2020).