Evidence-based expert consensus on clinical management of safety of Bruton's tyrosine kinase inhibitors (2024)

Abstract

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

Keywords: BTK inhibitors; Consensus; adverse drug events; drug-drug interactions; safety.

Figure 1

Overall framework for clinical safety management of BTKis. BTKis, Bruton’s tyrosine kinase inhibitors.

Figure 2

Whole-process clinical management strategy for BTKi-related bleeding. BTKis, Bruton’s tyrosine kinase inhibitors; Etc, etcetera; NSAIDs, nonsteroidal anti-inflammatory drugs; TBIP, Thromboembolic risk, Bleeding risk, drug-drug Interactions, and Patient preferences; NOAC, non-vitamin K antagonist oral anticoagulant; LMWH, low molecular weight heparin; DAPT, double antiplatelet drug therapy; Eg, exempli gratia.

Figure 3

Whole-process clinical management strategy for BTKi-related cardiovascular events. BTKis, Bruton’s tyrosine kinase inhibitors; MDT, multi-disciplinary treatment; TBIP, Thromboembolic risk, Bleeding risk, drug-drug Interactions, and Patient preferences; CYP, cytochrome P450; P-gp, P-glycoprotein.

Figure 4

Clinical management strategy for BTKi-related hematological toxicity. BTKi, Bruton’s tyrosine kinase inhibitor.

Figure 5

Clinical management strategy for BTKi-related rash. BTKi, Bruton’s tyrosine kinase inhibitor; PDGFR, platelet-derived growth factor receptor; EGFR, epidermal growth factor receptor.