Acalabrutinib May Be Safe, Effective for Relapsed CLL
Acalabrutinib had promising safety and efficacy profiles in patients with relapsed chronic lymphocytic leukemia.
Acalabrutinib had promising safety and efficacy profiles in patients with relapsed chronic lymphocytic leukemia (CLL), including those with chromosome 17p13.1 deletion, a recent study published online ahead of print in The New England Journal of Medicine has shown.1
Although irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents a significant advancement in the treatment of CLL, it also irreversibly blocks other kinase targets that may ultimately compromise its therapeutic potential.
Therefore, researchers sought to evaluate the safety and efficacy of acalabrutinib, a more selective, irreversible BTK inhibitor that is specifically designed to be safer and more efficacious compared with first-generation BTK inhibitors.
For the multicenter, phase 1/2 study, researchers enrolled 61 patients with relapsed CLL. Of those, 31% had chromosome 17p13.1 deletion and 75% had unmutated immunoglobulin heavy-chain variable genes. Patients received acalabrutinib at a dose of 100 mg to 400 mg orally once daily in the phase 1 dose-escalation portion, and then 100 mg twice daily in the phase 2 expansion portion.
Results showed that at a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis. The remaining 5% of patients had stable disease.
Researchers found that the overall response rate was 100% among participants with chromosome 17p13.1 deletion. Of note, there were no instances of Richter's formation, and only 1 case of CLL progression occurred.
In terms of safety, the most common adverse events were headache, diarrhea, and increased weight. Most adverse events were grade 1 or 2 and no dose-limiting toxicities occurred during phase 1.
- Byrd JC, Harrington B, O'Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia [published online ahead of print December 7, 2015].N Engl J Med. doi: 10.1056/NEJMoa1509981.