PMID- 35196370
OWN - NLM
STAT- MEDLINE
DCOM- 20220606
LR  - 20240425
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 139
IP  - 22
DP  - 2022 Jun 2
TI  - Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary 
      analysis of the CAPTIVATE FD cohort.
PG  - 3278-3289
LID - 10.1182/blood.2021014488 [doi]
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.
CI  - (c) 2022 by The American Society of Hematology.
FAU - Tam, Constantine S
AU  - Tam CS
AUID- ORCID: 0000-0002-9759-5017
AD  - Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
AD  - St. Vincent's Hospital, Melbourne, VIC, Australia.
AD  - University of Melbourne, Melbourne, VIC, Australia.
FAU - Allan, John N
AU  - Allan JN
AUID- ORCID: 0000-0002-2088-0899
AD  - Weill Cornell Medicine, New York, NY.
FAU - Siddiqi, Tanya
AU  - Siddiqi T
AUID- ORCID: 0000-0001-5292-8298
AD  - City of Hope National Medical Center, Duarte, CA.
FAU - Kipps, Thomas J
AU  - Kipps TJ
AD  - Moores Cancer Center, University of California San Diego, San Diego, CA.
FAU - Jacobs, Ryan
AU  - Jacobs R
AD  - Levine Cancer Institute, Charlotte, NC.
FAU - Opat, Stephen
AU  - Opat S
AD  - Monash University, Clayton, VIC, Australia.
FAU - Barr, Paul M
AU  - Barr PM
AUID- ORCID: 0000-0002-9733-401X
AD  - Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY.
FAU - Tedeschi, Alessandra
AU  - Tedeschi A
AD  - ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
FAU - Trentin, Livio
AU  - Trentin L
AUID- ORCID: 0000-0003-1222-6149
AD  - University of Padova, Padova, Italy.
FAU - Bannerji, Rajat
AU  - Bannerji R
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.
FAU - Jackson, Sharon
AU  - Jackson S
AUID- ORCID: 0000-0003-3584-8872
AD  - Middlemore Hospital, Auckland, New Zealand.
FAU - Kuss, Bryone J
AU  - Kuss BJ
AD  - Flinders University and Medical Center, Bedford Park, SA, Australia.
FAU - Moreno, Carol
AU  - Moreno C
AD  - Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, 
      Barcelona, Spain.
FAU - Szafer-Glusman, Edith
AU  - Szafer-Glusman E
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Russell, Kristin
AU  - Russell K
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Zhou, Cathy
AU  - Zhou C
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Ninomoto, Joi
AU  - Ninomoto J
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Dean, James P
AU  - Dean JP
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Wierda, William G
AU  - Wierda WG
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX.
FAU - Ghia, Paolo
AU  - Ghia P
AUID- ORCID: 0000-0003-3750-7342
AD  - Universita Vita-Salute San Raffaele, Milan, Italy; and.
AD  - IRCCS Ospedale San Raffaele, Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Piperidines)
RN  - 0 (Sulfonamides)
RN  - 1X70OSD4VX (ibrutinib)
RN  - JAC85A2161 (Adenine)
RN  - N54AIC43PW (venetoclax)
SB  - IM
CIN - Blood. 2022 Jun 2;139(22):3229-3230. PMID: 35653166
MH  - Adenine/analogs & derivatives
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell
MH  - Neoplasm, Residual/etiology
MH  - Piperidines
MH  - Sulfonamides
PMC - PMC11022982
EDAT- 2022/02/24 06:00
MHDA- 2022/06/07 06:00
PMCR- 2022/02/25
CRDT- 2022/02/23 17:12
PHST- 2021/10/20 00:00 [received]
PHST- 2022/02/11 00:00 [accepted]
PHST- 2022/02/24 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/02/23 17:12 [entrez]
PHST- 2022/02/25 00:00 [pmc-release]
AID - S0006-4971(22)00246-4 [pii]
AID - 10.1182/blood.2021014488 [doi]
PST - ppublish
SO  - Blood. 2022 Jun 2;139(22):3278-3289. doi: 10.1182/blood.2021014488.