Acalabrutinib monotherapy in patients with relapsed/ refractory chronic lymphocytic leukemia: Updated phase 2 results

John C. Byrd, William G. Wierda, Anna Schuh, Stephen Devereux, Jorge M. Chaves, Jennifer R. Brown, Peter Hillmen, Peter Martin, Farrukh T. Awan, Deborah M. Stephens, Paolo Ghia, Jacqueline Barrientos, John M. Pagel, Jennifer A. Woyach, Kathleen Burke, Todd Covey, Michael Gulrajani, Ahmed Hamdy, Raquel Izumi, Melanie M. FrigaultPriti Patel, Wayne Rothbaum, Min Hui Wang, Susan O'Brien, Richard R. Furman

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Therapeutic targeting of Bruton tyrosine kinase (BTK) has dramatically improved survival outcomes for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Acalabrutinib is an oral, highly selective BTK inhibitor that allows for twice-daily dosing due to its selectivity. In this phase 1b/2 study, 134 patients with relapsed/ refractory CLL or SLL (median age, 66 years [range, 42-85 years]; median prior therapies, 2 [range, 1-13]) received acalabrutinib 100 mg twice daily for a median of 41 months (range, 0.2-58 months). Median trough BTK occupancy at steady state was 97%. Most adverse events (AEs) were mild or moderate, and were most commonly diarrhea (52%) and headache (51%). Grade ‡3 AEs (occurring in ‡5% of patients) were neutropenia (14%), pneumonia (11%), hypertension (7%), anemia (7%), and diarrhea (5%). Atrial fibrillation and major bleeding AEs (all grades) occurred in 7% and 5% of patients, respectively. Most patients (56%) remain on treatment; the primary reasons for discontinuation were progressive disease (21%) and AEs (11%). The overall response rate, including partial response with lymphocytosis, with acalabrutinib was 94%; responses were similar regardless of genomic features (presence of del(11)(q22.3), del(17)(p13.1), complex karyotype, or immunoglobulin variable region heavy chain mutation status). Median duration of response and progression-free survival (PFS) have not been reached; the estimated 45-month PFS was 62% (95% confidence interval, 51% to 71%). BTK mutation was detected in 6 of 9 patients (67%) at relapse. This updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation in previously untreated and treated patients with CLL/SLL.

Original languageEnglish (US)
Pages (from-to)1204-1213
Number of pages10
Issue number15
StatePublished - Apr 9 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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