Cutaneous Adverse Effects in Patients Treated with BTK Inhibitors

Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles.