A Novel Two-Part Mixture Model for the Incidence and Time Course of Cytokine Release Syndrome After Elranatamab Dosing in Multiple Myeloma Patients.

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Tác giả: Mohamed Elmeliegy, Jennifer Hibma, Donald Irby, Kamrine Poels, Blerta Shtylla, Erik Vandendries, Diane Wang, Jason H Williams

Ngôn ngữ: eng

Ký hiệu phân loại: 641.5612 Cooking

Thông tin xuất bản: United States : Clinical pharmacology and therapeutics , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 163050

Cytokine release syndrome (CRS) is a common, acute adverse event associated with T-cell redirecting therapies such as bispecific antibodies (BsAbs). The nature of CRS events data makes it challenging to capture an unbiased exposure-response relationship with commonly used models. For example, simple logistic regression models cannot handle traditional time-varying exposure, and static exposure metrics chosen at early time points and with lower priming doses may underestimate the incidence of CRS. Therefore, more advanced modeling techniques are needed to adequately describe the time course of BsAb-induced CRS. Herein, we present a two-part mixture model that describes the population incidence and time course of CRS following various dose-priming regimens of elranatamab, a humanized BsAb that targets the B-cell maturation antigen on myeloma cells and CD3 on T cells, where the conditional time-evolution of CRS was described with a two-state (i.e., CRS-yes or no) Markov model. In the first part, increasing elranatamab exposure (maximum elranatamab concentration at first CRS event time (C
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