Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF‐α experience to oncology

Abstract

Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM.

Why therapeutic drug monitoring is needed for monoclonal antibodies and how do we implement this?

“…In the current review describing the need for therapeutic drug monitoring (TDM) in inflammatory and malignant disease treated with mAbs, 4 the authors cite significant between-subject variability (BSV) reported for various mAbs (e.g., BSV for infliximab clearance of 34%; BSV for trastuzumab clearance 43%).…”

“…Similar benefits from TDM have been shown in other inflammatory diseases 7 with other anti-TNF agents (see ref. 4 for more information). Although TDM is not specifically recommended in package inserts for mAbs used to treat inflammatory diseases, it has nonetheless become an important component of therapy.…”

“…In solid tumors, the clearance of bevacizumab in advanced gastric cancer was also found to be higher than in patients with less advanced disease. 9 Other cases in which mAb clearance is impacted by tumor burden have been reported, 4 suggesting similarly variable pharmacokinetics in mAbs use to treat a wide range of solid and hematologic tumors. In these studies, low mAb trough concentrations were associated with poor prognosis, supporting the potential for TDM as a tool to improve outcomes.…”

“…In the current review of TDM in inflammatory and malignant disease, 4 the authors cite a number of hurdles that must be overcome before TDM can be implemented in routine clinical care, which are reflective of the types of evaluations usually carried out during routine drug development. These hurdles include conducting prospective clinical trials for each mAb and therapeutic indication to establish the exposureresponse relationship and developing a range of trough concentrations associated with response.…”

Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

“…If the patient has a low MAb concentration in the presence of ADAs, the physician may switch the patient to another MAb in the same class, or it may be necessary to switch the patient to therapy with a different target (15). For other MAbs outside the IBD setting, comprehensive studies showing the links among MAb concentrations, loss of response, and outcomes are not available and the recommendations for patient management based on serum monitoring of MAb concentrations is less clear, although it seems that the TNF-α inhibitor experience can be translated to other areas (21, 22). …”