TY - JOUR
T1 - Zanubrutinib for treatment-naïve and relapsed/refractory chronic lymphocytic leukaemia
T2 - long-term follow-up of the phase I/II AU-003 study
AU - Cull, Gavin
AU - Burger, Jan A.
AU - Opat, Stephen
AU - Gottlieb, David
AU - Verner, Emma
AU - Trotman, Judith
AU - Marlton, Paula
AU - Munoz, Javier
AU - Johnston, Patrick
AU - Simpson, David
AU - Stern, Jennifer C.
AU - Prathikanti, Radha
AU - Wu, Kenneth
AU - Novotny, William
AU - Huang, Jane
AU - Tam, Constantine S.
N1 - Publisher Copyright:
© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
PY - 2022/3
Y1 - 2022/3
N2 - The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response at 3 years was reported in 85·7%. The ORR in patients with del(17p)/tumour protein p53 mutation was 87·5% (CR 16·7%). The 2- and 3-year progression-free survival estimates were 90% (TN, 90%; R/R, 91%) and 83% (TN, 81%; R/R, 83%) respectively. The most reported Grade ≥3 adverse events were neutropenia (15·4%), pneumonia (9·8%), hypertension (8·9%) and anaemia (6·5%). The annual incidence of atrial fibrillation, major haemorrhage, Grade ≥3 neutropenia and Grade ≥3 infection decreased over time. With a median follow-up of ~4 years, responses remain clinically meaningful and durable and long-term tolerability to zanubrutinib therapy continues.
AB - The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response at 3 years was reported in 85·7%. The ORR in patients with del(17p)/tumour protein p53 mutation was 87·5% (CR 16·7%). The 2- and 3-year progression-free survival estimates were 90% (TN, 90%; R/R, 91%) and 83% (TN, 81%; R/R, 83%) respectively. The most reported Grade ≥3 adverse events were neutropenia (15·4%), pneumonia (9·8%), hypertension (8·9%) and anaemia (6·5%). The annual incidence of atrial fibrillation, major haemorrhage, Grade ≥3 neutropenia and Grade ≥3 infection decreased over time. With a median follow-up of ~4 years, responses remain clinically meaningful and durable and long-term tolerability to zanubrutinib therapy continues.
KW - Bruton tyrosine kinase
KW - chromosome 17p deletion
KW - chronic lymphocytic leukaemia
KW - small lymphocytic lymphoma
KW - zanubrutinib
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U2 - 10.1111/bjh.17994
DO - 10.1111/bjh.17994
M3 - Article
C2 - 34915592
AN - SCOPUS:85121364930
SN - 0007-1048
VL - 196
SP - 1209
EP - 1218
JO - British journal of haematology
JF - British journal of haematology
IS - 5
ER -