Evaluation of infectious morbidity due to BTK inhibitors in indolent B-cell lymphomas: latest research findings and systematic analysis

Abstract

Introduction: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis of this topic as derived from RCTs and clinical practice is needed.

Areas covered: An extensive Medline, Embase, and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1 January 2014 - 31 December 2023). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered.

Expert opinion: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1-2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1^st, 2^nd and 3^rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes.

Keywords: BTK inhibitors; acalabrutinib; ibrutinib; immune defect; infections; low-grade B-cell lymphomas; pirtobrutinib; zanubrutinib.