Acalabrutinib for Resistant CLL: Therapeutic Option for Ibrutinib-Intolerant Patients?
Posted: Thursday, April 8, 2021
A recent study found that the Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may be an effective and tolerable alternative for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who cannot tolerate ibrutinib. Kerry A. Rogers, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues noted that acalabrutinib might allow more patients with CLL to benefit from BTK inhibitor therapy.
In this phase II trial, published in Haematologica, 60 patients (median age, 69.5 years) received oral acalabrutinib at 100 mg twice daily until disease progression or intolerance. The overall response rate to acalabrutinib was 73%, and three patients achieved complete remission. For those patients who had del(17p), the overall response rate was 71%.
As for toxicity, the most frequent adverse events reported with acalabrutinib were diarrhea (53%), headache (42%), contusion (40%), dizziness (33%), upper respiratory tract infection (33%), and cough (30%). In addition, the most common reasons for acalabrutinib discontinuation were progressive disease and adverse events. The researchers emphasized that most patients with baseline samples (49 of 52; 94%) and all with on-treatment samples (3 of 3; 100%) had no detectable BTK and/or PLCG2 mutations.
A total of 17 patients (28%) had del(17p), and 31 patients (52%) had Rai stage III or IV disease. To determine whether mutations associated with resistance to BTK inhibitors were present before acalabrutinib treatment, purified B-cell samples at the start of acalabrutinib treatment were tested for mutations in BTK and PLCG2. Of the two patients with mutations associated with BTK and/or PCLG2, one was electively taken off acalabrutinib after about 2 months of exposure and was not evaluable for response to acalabrutinib. The other patient received acalabrutinib and had progressive disease after 15 months, achieving a best response of stable disease.
Disclosure: For full disclosures of the study authors, visit haematologica.org.
