Acalabrutinib treatment for ibrutinib-intolerant patients with relapsed/refractory chronic lymphocytic leukemia

This study aimed to investigate if acalabrutinib (Calquence) was suitable for patients with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) who are intolerant to ibrutinib (Imbruvica).  

This study concluded that acalabrutinib was effective and well tolerated in these patients.  

Ibrutinib is a type of targeted therapy known as a Bruton tyrosine kinase (BTK) inhibitor. It is very effective in the treatment of CLL. However, ibrutinib may cause intolerable side effects for some patients. Other treatment options are needed for these patients.

Acalabrutinib is another BTK inhibitor. It is also approved for the treatment of patients with CLL. It has shown fewer side effects compared to ibrutinib. However, it was unknown if acalabrutinib would be better tolerated by patients with r/r CLL who are intolerant to ibrutinib. 

This study involved 60 patients with r/r CLL who were intolerant to ibrutinib and had continued disease activity. Patients were treated with acalabrutinib 100mg twice daily until disease progression or intolerance. Patients were followed up for an average of 34.6 months. 

The overall response rate to acalabrutinib was 73%. 5% of patients achieved complete remission (CR). After 2 years, 81% of patients were still responding to treatment. 

At 24 months, 72% of patients were estimated to remain free of disease and 81% were estimated to be alive.  

53% of patients experienced diarrhea as a side effect. 42% experienced headache and 40% had contusion (bruising). Serious side effects were reported in 52% of patients. 17% of these were considered related to acalabrutinib treatment. The most common reasons for stopping acalabrutinib treatment were progressive disease and side effects.

This study concluded that acalabrutinib is effective and well tolerated in patients with r/r CLL who were intolerant to ibrutinib.    

The response to previous ibrutinib treatment was not well studied. Also, the number of participants was very small. This study was funded by AstraZeneca, the manufacturer of acalabrutinib.