Related Experiment Video
Updated: Mar 29, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia
John C Byrd1, Bonnie Harrington, Susan O'Brien
1From the Division of Hematology, Department of Internal Medicine, Ohio State University (J.C. Byrd, J.A.J., F.T.A., J.W., A.J.J.), and the Department of Veterinary Biosciences, College of Veterinary Medicine (B.H.) - both in Columbus; UC Irvine Health Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange (S.O.); University of Oxford, Oxford (A.S.), NHS Foundation Trust, King's College Hospital, London (S.D.), and the Department of Haematology, St. James's University Hospital, Leeds (P.H.) - all in the United Kingdom; Northwest Medical Specialties, Tacoma (J.C.), and the Swedish Cancer Institute, Seattle (J.M.P.) - both in Washington; the Department of Leukemia, Division of Cancer Medicine, University of Texas, and M.D. Anderson Cancer Center - both in Houston (W.G.W.); the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston (J.R.B.); Huntsman Cancer Institute, University of Utah, Salt Lake City (D.M.S.); Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milan (P.G.); Hofstra North Shore-LIJ School of Medicine, Chronic Lymphocytic Leukemia Research and Treatment Center, Lake Success (J.C. Barrientos), and the Department of Pathology and Cell Biology, Columbia University Medical Center (T.G.D.), and New York-Presbyterian/Weill Cornell Medical Center, New York (R.R.F.) - all in New York; and Acerta Pharma, Oss, the Netherlands (D.J., J.H., X.W., A.K., B.J.L., T.C., M.F., J.M., A.H., W.R., R.I.).
Background:
Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.
Methods:
In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion.
Results:
The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. 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. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred.
Conclusions:
In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443.).
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents