Population Pharmacokinetics for Belantamab Mafodotin Monotherapy and Combination Therapies in Patients with Relapsed/Refractory Multiple Myeloma

The study developed updated population pharmacokinetic (PopPK) models for the antibody–drug conjugate belantamab mafodotin and its cytotoxic payload cys-mcMMAF in patients with relapsed/refractory multiple myeloma, using pooled data from six clinical trials. Both were best described by linear two-compartment models, with belantamab mafodotin showing time-dependent clearance decreases—more pronounced with combination therapy—resulting in longer half-lives. Key covariates affecting pharmacokinetics included disease burden markers (e.g., soluble BCMA, serum IgG), albumin, body weight, BMI, race, and treatment type, while renal or hepatic impairment, age, ethnicity, geographic region, and prior therapies had no meaningful impact. Importantly, combination therapy did not significantly change early drug exposure compared with monotherapy, and higher disease burden was associated with lower initial exposure. These findings help refine dosing strategies and support the drug’s use across diverse patient populations.