Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B‐cell non‐Hodgkin lymphoma

• DOI: 10.1111/cts.13825
• Publication Date: 2024-05-29T09:30:35Z
• Authors: Brendan Bender; Chi‐Chung Li; Mathilde Marchand; David C. Turner; Feifei Li; Shweta Vadhavkar; Bei Wang; Rong Deng; James Lu; Jin Jin; Chunze Li; Shen Yin; Michael Wei; Pascal Chanu
• Keywords: Obinutuzumab; Refractory (planetary science); Cytokine Release Syndrome; Regimen

Abstract Mosunetuzumab (Mosun) is a CD20xCD3 T‐cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step‐up dose regimen of 1/2/60/30 mg IV designed mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed/refractory B‐Cell Non‐Hodgkin lymphoma receiving Mosun monotherapy, including fixed dosing (0.05–2.8 every 3 weeks (q3w)) Cycle 1 groups (0.4/1/2.8–1/2/60/30 q3w). Prior treatment, ~50% had residual levels anti‐CD20 drugs (e.g., rituximab or obinutuzumab) prior treatment. CD20 receptor binding dynamics rituximab/obinutuzumab PK were incorporated into the calculate occupancy percentage (RO%) over time. two‐compartment time‐dependent clearance (CL) best described data. typical patient an initial CL 1.08 L/day, transitioning steady‐state 0.584 L/day. Statistically relevant covariates on parameters included body weight, albumin, sex, tumor burden, baseline drug concentration; no covariate found have clinically impact exposure at dose. RO% highly variable, attributed large variability concentration (median = 10 μg/mL). 60 loading doses increased 1, providing efficacious exposures presence competing drugs. PopPK simulations, investigating delays, informed treatment resumption protocols ensure CRS mitigation.