TY - JOUR
T1 - Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
AU - Tam, Constantine S.
AU - Robak, Tadeusz
AU - Ghia, Paolo
AU - Kahl, Brad S.
AU - Walker, Patricia
AU - Janowski, Wojciech
AU - Simpson, David
AU - Shadman, Mazyar
AU - Ganly, Peter S.
AU - Laurenti, Luca
AU - Opat, Stephen
AU - Tani, Monica
AU - Ciepluch, Hanna
AU - Verner, Emma
AU - Šimkovič, Martin
AU - Österborg, Anders
AU - Trněný, Marek
AU - Tedeschi, Alessandra
AU - Paik, Jason C.
AU - Kuwahara, Sowmya B.
AU - Feng, Shibao
AU - Ramakrishnan, Vanitha
AU - Cohen, Aileen
AU - Huang, Jane
AU - Hillmen, Peter
AU - Brown, Jennifer R.
N1 - Publisher Copyright:
©2021 Ferrata Storti Foundation
PY - 2021/9
Y1 - 2021/9
N2 - Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase III SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42–86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0–26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI: 79.0–94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI: 88.4–98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥ 3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered as clinicaltrials.gov Identifier: NCT03336333.
AB - Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase III SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42–86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0–26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI: 79.0–94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI: 88.4–98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥ 3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered as clinicaltrials.gov Identifier: NCT03336333.
UR - http://www.scopus.com/inward/record.url?scp=85093538653&partnerID=8YFLogxK
U2 - 10.3324/haematol.2020.259432
DO - 10.3324/haematol.2020.259432
M3 - Article
C2 - 33054121
AN - SCOPUS:85093538653
SN - 0390-6078
VL - 106
SP - 2354
EP - 2363
JO - Haematologica
JF - Haematologica
IS - 9
ER -