Acalabrutinib vs. ibrutinib: How do they compare?

Acalabrutinib, a treatment for chronic lymphocytic leukemia (CLL), appears to have a lower risk of adverse events (such as atrial fibrillation) in comparison to ibrutinib. A 2021 phase III study in the Journal of Clinical Oncology found that while both medications have similar efficacy, acalabrutinib was better tolerated with fewer side effects. In clinical studies:

• In comparison to ibrutinib, acalabrutinib was associated with an overall lower occurrence rate of hypertension, diarrhea, arthralgia, atrial fibrillation, back pain, urinary tract infection, muscle spasms, bruising and indigestion.
• In comparison to ibrutinib, acalabrutinib was associated with an overall higher occurrence rate of headache, cough and fatigue.

• A grade 3 or higher infection developed similarly for both drugs: 30% of ibrutinib patients in comparison to 30.8% of acalabrutinib patients developed these infections.

• The most common serious side effects for both acalabrutinib and ibrutinib were found to be anemia, pneumonia and atrial fibrillation.

Researchers have found that acalabrutinib is a more selective Bruton’s tyrosine kinase (BTK) inhibitor. The way that both acalabrutinib and ibrutinib work is by irreversibly binding to and destroying the cancerous B lymphocytes. Acalabrutinib’s increased selectivity means that the risk of off-target cells, or noncancerous cells, is much lower than in ibrutinib, which thus results in a lower risk of adverse effects.