Model‐Based Determination of Elotuzumab Pharmacokinetics in Japanese Patients With Multiple Myeloma Incorporating Time‐Varying M Protein

A population pharmacokinetic model was developed to evaluate the effects of Japanese ethnicity, prior line of therapy (0 or ≥1), time‐varying M protein, and maintenance dosing regimens (10 mg/kg intravenously every 2 weeks or 20 mg/kg intravenously every 4 weeks beginning in cycle 19) on the pharmacokinetics of elotuzumab in patients with multiple myeloma treated with elotuzumab plus lenalidomide/dexamethasone. Elotuzumab pharmacokinetics were characterized by a 2‐compartment model with parallel linear (nonspecific) and Michaelis‐Menten elimination from the central compartment and target‐mediated elimination from the peripheral compartment. Asian race on nonspecific clearance (CL) and central volume of distribution, prior line of therapy on CL, and maximum target‐mediated elimination rate (V max ) were statistically significant but not considered clinically relevant (magnitude < 20%). Time‐varying M protein on V max was statistically significant, and the magnitude was >20%; however, clinical implications in the setting of combination therapy were not expected. Model‐predicted steady‐state elotuzumab exposure in cycle 12 were similar in Japanese and non‐Japanese patients and in Japanese patients with 0 and ≥1 prior lines of therapy. Elotuzumab 20 mg/kg intravenously every 4 weeks beginning in cycle 19 produced time‐averaged concentrations similar to elotuzumab 10 mg/kg intravenously every 2 weeks, although maximum and minimum concentrations after elotuzumab 20 mg/kg intravenous every‐4‐week dosing were slightly higher and lower, respectively. In conclusion, the current analysis demonstrates that Japanese ethnicity, prior line of therapy, time‐varying M protein, and change in elotuzumab dosing regimen in cycle 19 have no clinically meaningful impact on elotuzumab pharmacokinetics and exposure in Japanese patients with multiple myeloma.