TY - JOUR
T1 - Effective Tumor Debulking with Ibrutinib Before Initiation of Venetoclax
T2 - Results from the CAPTIVATE Minimal Residual Disease and Fixed-Duration Cohorts
AU - Barr, Paul M.
AU - Tedeschi, Alessandra
AU - Wierda, William G.
AU - Allan, John N.
AU - Ghia, Paolo
AU - Vallisa, Daniele
AU - Jacobs, Ryan
AU - O'Brien, Susan
AU - Grigg, Andrew P.
AU - Walker, Patricia
AU - Zhou, Cathy
AU - Ninomoto, Joi
AU - Krigsfeld, Gabriel
AU - Tam, Constantine S.
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/10/15
Y1 - 2022/10/15
N2 - Purpose: The phase II CAPTIVATE study investigated firstline treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts. Patients and Methods: In both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). Results: In the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance <80 mL/minute) from 43% to 18%. Laboratory TLS perHoward criteria occurred in one patient; no clinicalTLS was observed. Conclusions: Three cycles of ibrutinib lead-in before venetoclax initiation provides effective tumor debulking, decreases the TLS risk category and reduces the need for hospitalization for intensive monitoring for TLS.
AB - Purpose: The phase II CAPTIVATE study investigated firstline treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts. Patients and Methods: In both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). Results: In the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance <80 mL/minute) from 43% to 18%. Laboratory TLS perHoward criteria occurred in one patient; no clinicalTLS was observed. Conclusions: Three cycles of ibrutinib lead-in before venetoclax initiation provides effective tumor debulking, decreases the TLS risk category and reduces the need for hospitalization for intensive monitoring for TLS.
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U2 - 10.1158/1078-0432.CCR-22-0504
DO - 10.1158/1078-0432.CCR-22-0504
M3 - Article
C2 - 35939599
AN - SCOPUS:85139880640
SN - 1078-0432
VL - 28
SP - 4385
EP - 4391
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -