TY - JOUR
T1 - Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL
T2 - primary analysis of the CAPTIVATE FD cohort
AU - Tam, Constantine S.
AU - Allan, John N.
AU - Siddiqi, Tanya
AU - Kipps, Thomas J.
AU - Jacobs, Ryan
AU - Opat, Stephen
AU - Barr, Paul M.
AU - Tedeschi, Alessandra
AU - Trentin, Livio
AU - Bannerji, Rajat
AU - Jackson, Sharon
AU - Kuss, Bryone J.
AU - Moreno, Carol
AU - Szafer-Glusman, Edith
AU - Russell, Kristin
AU - Zhou, Cathy
AU - Ninomoto, Joi
AU - Dean, James P.
AU - Wierda, William G.
AU - Ghia, Paolo
N1 - Funding Information:
The authors thank all the patients who participated in this study and their supportive families, as well as the investigators and clinical research staff from the study centers. The authors also thank Lisa J. Croner for her valuable contributions to bioinformatics analysis of next-generation sequencing data; Lisa J. Croner is an employee of AbbVie and owns AbbVie stock. This study was supported by Pharmacyclics LLC, an AbbVie Company. Medical writing support was provided by Melanie Sweetlove and funded by Pharmacyclics LLC, an AbbVie Company.
Funding Information:
This study was supported by Pharmacyclics LLC, an AbbVie Company. Medical writing support was provided by Melanie Sweetlove and funded by Pharmacyclics LLC, an AbbVie Company.
Publisher Copyright:
© 2022 American Society of Hematology
PY - 2022/6/2
Y1 - 2022/6/2
N2 - CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.
AB - CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.
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U2 - 10.1182/blood.2021014488
DO - 10.1182/blood.2021014488
M3 - Article
C2 - 35196370
AN - SCOPUS:85127788631
SN - 0006-4971
VL - 139
SP - 3278
EP - 3289
JO - Blood
JF - Blood
IS - 22
ER -