PMID- 35427411
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20240207
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 140
IP  - 2
DP  - 2022 Jul 14
TI  - Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated 
      results of the E1912 trial.
PG  - 112-120
LID - 10.1182/blood.2021014960 [doi]
AB  - Herein, we present the long-term follow-up of the randomized E1912 trial 
      comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to 
      fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability 
      of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naive patients 
      aged </=70 years with chronic lymphocytic leukemia (CLL). Patients were randomly 
      assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 
      5.8 years, median progression-free survival (PFS) is superior for IR (hazard 
      ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with 
      both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 
      0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .001). Among the 354 
      patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 
      138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who 
      started IR) discontinued therapy due to disease progression or death, 77 (21.9% 
      of patients who started IR) discontinued therapy for adverse events 
      (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other 
      reasons. Progression was uncommon among patients able to remain on ibrutinib. The 
      median time from ibrutinib discontinuation to disease progression or death among 
      those who discontinued treatment for a reason other than progression was 25 
      months. Sustained improvement in overall survival (OS) was observed for patients 
      in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS 
      relative to FCR in patients with IGHV mutated or unmutated CLL, as well as 
      superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the 
      majority of CLL patients. This trial was registered at www.clinicaltrials.gov as 
      #NCT02048813.
CI  - (c) 2022 by The American Society of Hematology.
FAU - Shanafelt, Tait D
AU  - Shanafelt TD
AD  - Stanford University, Stanford, CA.
FAU - Wang, Xin Victoria
AU  - Wang XV
AD  - Dana Farber Cancer Institute, Boston, MA.
FAU - Hanson, Curtis A
AU  - Hanson CA
AD  - Mayo Clinic, Rochester, MN.
FAU - Paietta, Elisabeth M
AU  - Paietta EM
AD  - Montefiore Medical Center, Bronx, NY.
FAU - O'Brien, Susan
AU  - O'Brien S
AUID- ORCID: 0000-0002-2481-7504
AD  - University of California Irvine Medical Center, Irvine, CA.
FAU - Barrientos, Jacqueline
AU  - Barrientos J
AD  - Northwell Health/Center for Advanced Medicine, New Hyde Park, NY.
FAU - Jelinek, Diane F
AU  - Jelinek DF
AD  - Mayo Clinic, Rochester, MN.
FAU - Braggio, Esteban
AU  - Braggio E
AUID- ORCID: 0000-0003-3860-4830
AD  - Mayo Clinic, Rochester, MN.
FAU - Leis, Jose F
AU  - Leis JF
AD  - Mayo Clinic, Rochester, MN.
FAU - Zhang, Cong Christine
AU  - Zhang CC
AD  - Kaiser Permanente NCORP/The Permanente Medical Group, Fresno, CA.
FAU - Coutre, Steven E
AU  - Coutre SE
AD  - Stanford University, Stanford, CA.
FAU - Barr, Paul M
AU  - Barr PM
AUID- ORCID: 0000-0002-9733-401X
AD  - Rochester University, Rochester, NY.
FAU - Cashen, Amanda F
AU  - Cashen AF
AD  - Washington University School of Medicine, St. Louis, MO.
FAU - Mato, Anthony R
AU  - Mato AR
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY.
FAU - Singh, Avina K
AU  - Singh AK
AD  - Minnesota Oncology, Burnsville, MN.
FAU - Mullane, Michael P
AU  - Mullane MP
AD  - Aurora Cancer Care, Milwaukee West, Milwaukee, WI.
FAU - Little, Richard F
AU  - Little RF
AUID- ORCID: 0000-0002-4091-1699
AD  - National Cancer Institute, Bethesda, MD; and.
FAU - Erba, Harry
AU  - Erba H
AUID- ORCID: 0000-0003-1093-2189
AD  - Duke University, Durham, NC.
FAU - Stone, Richard M
AU  - Stone RM
AD  - Dana Farber Cancer Institute, Boston, MA.
FAU - Litzow, Mark
AU  - Litzow M
AUID- ORCID: 0000-0002-9816-6302
AD  - Mayo Clinic, Rochester, MN.
FAU - Tallman, Martin
AU  - Tallman M
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY.
FAU - Kay, Neil E
AU  - Kay NE
AUID- ORCID: 0000-0002-5951-5055
AD  - Mayo Clinic, Rochester, MN.
LA  - eng
SI  - ClinicalTrials.gov/NCT02048813
GR  - R01 CA193541/CA/NCI NIH HHS/United States
GR  - UG1 CA233290/CA/NCI NIH HHS/United States
GR  - UG1 CA233230/CA/NCI NIH HHS/United States
GR  - UG1 CA190140/CA/NCI NIH HHS/United States
GR  - UG1 CA189859/CA/NCI NIH HHS/United States
GR  - U24 CA196172/CA/NCI NIH HHS/United States
GR  - U10 CA180821/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - UG1 CA232760/CA/NCI NIH HHS/United States
GR  - UG1 CA189863/CA/NCI NIH HHS/United States
GR  - UG1 CA233180/CA/NCI NIH HHS/United States
GR  - P30 CA014236/CA/NCI NIH HHS/United States
GR  - U10 CA180794/CA/NCI NIH HHS/United States
GR  - U10 CA180888/CA/NCI NIH HHS/United States
GR  - UG1 CA233339/CA/NCI NIH HHS/United States
GR  - U10 CA180820/CA/NCI NIH HHS/United States
GR  - U10 CA180833/CA/NCI NIH HHS/United States
GR  - UG1 CA233253/CA/NCI NIH HHS/United States
GR  - U10 CA180867/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Immunoglobulin Variable Region)
RN  - 0 (Piperidines)
RN  - 1X70OSD4VX (ibrutinib)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - JAC85A2161 (Adenine)
SB  - IM
CIN - Blood. 2022 Jul 14;140(2):80-81. PMID: 35834283
MH  - Adenine/analogs & derivatives
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Cyclophosphamide/adverse effects
MH  - Disease Progression
MH  - Humans
MH  - Immunoglobulin Variable Region
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/genetics
MH  - Piperidines
MH  - Rituximab/therapeutic use
MH  - Treatment Outcome
PMC - PMC9283968
EDAT- 2022/04/16 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/14
CRDT- 2022/04/15 17:09
PHST- 2021/11/29 00:00 [received]
PHST- 2022/03/25 00:00 [accepted]
PHST- 2022/04/16 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/04/15 17:09 [entrez]
PHST- 2022/07/14 00:00 [pmc-release]
AID - S0006-4971(22)00516-X [pii]
AID - 2022/BLD2021014960 [pii]
AID - 10.1182/blood.2021014960 [doi]
PST - ppublish
SO  - Blood. 2022 Jul 14;140(2):112-120. doi: 10.1182/blood.2021014960.