TY - JOUR
T1 - Acalabrutinib monotherapy in patients with relapsed/ refractory chronic lymphocytic leukemia
T2 - Updated phase 2 results
AU - Byrd, John C.
AU - Wierda, William G.
AU - Schuh, Anna
AU - Devereux, Stephen
AU - Chaves, Jorge M.
AU - Brown, Jennifer R.
AU - Hillmen, Peter
AU - Martin, Peter
AU - Awan, Farrukh T.
AU - Stephens, Deborah M.
AU - Ghia, Paolo
AU - Barrientos, Jacqueline
AU - Pagel, John M.
AU - Woyach, Jennifer A.
AU - Burke, Kathleen
AU - Covey, Todd
AU - Gulrajani, Michael
AU - Hamdy, Ahmed
AU - Izumi, Raquel
AU - Frigault, Melanie M.
AU - Patel, Priti
AU - Rothbaum, Wayne
AU - Wang, Min Hui
AU - O'Brien, Susan
AU - Furman, Richard R.
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/4/9
Y1 - 2020/4/9
N2 - 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.
AB - 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.
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U2 - 10.1182/BLOOD.2018884940
DO - 10.1182/BLOOD.2018884940
M3 - Article
C2 - 31876911
AN - SCOPUS:85078437992
SN - 0006-4971
VL - 135
SP - 1204
EP - 1213
JO - Blood
JF - Blood
IS - 15
ER -