Bruton tyrosine kinase (BTK) inhibitors represent an important therapeutic advancement for B cell malignancies. Ibrutinib, the first-in-class BTK inhibitor, is approved by the US FDA to treat patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL; after ≥1 prior therapy); and by the European Medicines Agency (EMA) for adult patients with relapsed/refractory (R/R) MCL and patients with CLL. Ibrutinib treatment can be limited by adverse events (AEs) including atrial fibrillation, arthralgias, rash, diarrhea, and bleeding events, leading to drug discontinuation in 4%-26% of patients. Acalabrutinib, a second-generation BTK inhibitor, is approved by the FDA to treat adult patients with CLL/SLL or MCL (relapsed after 1 prior therapy); and by the EMA to treat adult patients with CLL or R/R MCL. The most common AE associated with acalabrutinib is headache of limited duration, which occurs in 22%-51% of patients, and is mainly grade 1-2 in severity, with only 1% of patients experiencing grade ≥3 headache. Furthermore, acalabrutinib is associated with a low incidence of atrial fibrillation. Zanubrutinib, a selective next-generation covalent BTK inhibitor, is approved by the FDA to treat adult patients with MCL who have received ≥1 prior therapy, and is under investigation for the treatment of patients with CLL. In the phase 3 SEQUOIA trial in patients with CLL, the most common grade ≥3 AEs were neutropenia/neutrophil count decreased and infections. This review provides an overview of BTK inhibitor-related AEs in patients with CLL, and strategies for their management.
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http://dx.doi.org/10.3389/fonc.2021.720704 | DOI Listing |
Hematol Oncol
January 2025
Hematology, Oncology R&D, AstraZeneca, Cambridge, UK.
Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).
View Article and Find Full Text PDFWiad Lek
December 2024
STATE INSTITUTION OF SCIENCE ≪CENTER OF INNOVATIVE HEALTHCARE TECHNOLOGIES≫ STATE ADMINISTRATIVE DEPARTMENT, KYIV, UKRAINE.
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that affects the bone marrow, lymph nodes, and spleen, and is associated with certain complications. One of the complications of CLL is acquired immunodeficiency, leading to a predisposition for prolonged respiratory viral and bacterial infections. This publication presents a clinical case of a prolonged and severe course of COVID-19 in a patient with CLL, who was successfully treated with immunoglobulin replacement therapy.
View Article and Find Full Text PDFCureus
November 2024
Neurology, Mayo Clinic, Rochester, USA.
While earlier post-mortem studies show involvement of the central nervous system in 71% of patients with chronic lymphocytic leukemia (CLL), involvement intravitam is rare. A 72-year-old man with untreated, minimally symptomatic CLL developed subacute-onset encephalopathy and presented with severe hyponatremia and stress-induced cardiomyopathy. His initial head computed tomography scan was unremarkable.
View Article and Find Full Text PDFCancer Med
December 2024
Department of Haemato-Oncology, University Hospital Ostrava, Ostrava, Czech Republic.
Aims: To evaluate antibody response to mRNA vaccine, identify subgroups with poor response and to determine long-term antibody durability in hematological patients.
Materials And Methods: We have vaccinated 292 patients with all hematological malignancies with a third dose of mRNA COMIRNATY vaccine with a 12-month follow-up period in our center in Ostrava, Czech Republic.
Results: Antibody response for the whole cohort exceeded 74% through the whole 12-month follow-up.
Curr Probl Cardiol
December 2024
Cardiology Department. Reina Sofía University Hospital. Maimonides Institute for Biomedical Research of Córdoba (IMIBIC). Córdoba, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV). Carlos III Health Institute, Madrid, Spain.
Background: "Real-life" data on cardiovascular management and clinical outcomes in patients with atrial fibrillation (AF) and hematologic malignancies are limited.
Aim: To describe the clinical profile and incidence of cardiovascular events in this population.
Methods: Data were obtained from the CANAC-FA Registry, an observational, multicenter and retrospective study.
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