Acalabrutinib: A Favorable Safety Profile in BTK Inhibition
Prof Martin Dreyling discusses the safety profile of the BTK inhibitor acalabrutinib in patients with mantle cell lymphoma.
Acalabrutinib (Calquence), a second-generation Bruton tyrosine kinase (BTK) inhibitor, generally demonstrates a favorable safety profile, particularly when compared to earlier BTK inhibitors like ibrutinib (Imbruvica). Its increased selectivity for BTK is believed to contribute to a reduced incidence of certain off-target adverse events. Here, Prof Martin Dreyling, professor in the Department of Medicine in the University Hospital and head of the lymphoma program at the Department of Medicine III, LMU Hospital Munich, discusses the safety profile of the agent, especially as it relates to patients with mantle cell lymphoma.
Common adverse effects associated with acalabrutinib include headache, diarrhea, upper respiratory tract infection, musculoskeletal pain, and bruising. While these are often mild to moderate (grade 1 or 2) and may resolve with continued treatment, severe adverse events can occur.
Of particular note is its cardiovascular safety. Clinical trials have shown that acalabrutinib is associated with a lower incidence of cardiovascular-related toxicities, including atrial fibrillation/flutter and hypertension, compared to ibrutinib. This makes it a potentially more suitable option for patients with pre-existing cardiovascular conditions.
Regarding bleeding, acalabrutinib can cause hemorrhagic events, though major bleeding (serious or grade 3 or higher) is relatively uncommon. Bruising and petechiae are more frequently reported. Patients on concomitant antithrombotic agents may have an increased risk, and the benefits and risks of such co-administration should be carefully considered.
Infections, including serious and opportunistic infections, can occur with acalabrutinib, similar to other BTK inhibitors.Respiratory tract infections, including pneumonia, are among the most frequent. Patients with CLL, who often have compromised immune systems, may be at a higher risk of fungal infections. Regular monitoring for signs of infection is important.
Other potential adverse events include cytopenias (low blood cell counts like neutropenia, anemia, and thrombocytopenia) and second primary malignancies, with non-melanoma skin cancer being the most common. Liver function abnormalities have also been observed.
Overall, acalabrutinib offers a valuable therapeutic option with a generally manageable safety profile, particularly in its reduced cardiac toxicity compared to first-generation BTK inhibitors. Close monitoring for adverse events, especially bleeding, infections, and cardiac issues, remains crucial during treatment.
