PMID- 34274291
OWN - NLM
STAT- MEDLINE
DCOM- 20220216
LR  - 20220216
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 21
IP  - 11
DP  - 2021 Nov
TI  - Comparative Efficacy of First-Line Treatments of Chronic Lymphocytic Leukemia: 
      Network Meta-Analyses of Survival Curves.
PG  - e820-e831
LID - S2152-2650(21)00239-1 [pii]
LID - 10.1016/j.clml.2021.06.010 [doi]
AB  - BACKGROUND: Multiple treatment options in first-line chronic lymphocytic leukemia 
      (CLL) pose a challenge in identifying the best treatment. We performed novel 
      network meta-analyses (NMA; 8 trials, 11 treatments) on the Kaplan-Meier curves 
      to compare treatments for fludarabine-ineligible patients on progression-free 
      survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS). METHODS: 
      Using the Guyot method of enhanced secondary analysis of digitized survival data 
      and applying the fixed lognormal distribution model, we extracted the survival 
      proportions and hazard ratios (HR) over 60 months of follow-up, including PFS 
      comparisons by unmutated/mutated IGHV and del 17p. RESULTS: 
      Acalabrutinib-plus-obinutuzumab was associated with higher 5-year PFS proportions 
      than ibrutinib (HR = 0.42, 95% CrI = 0.25-0.63) but not acalabrutinib, 
      ibrutinib-plus-obinutuzumab, ibrutinib-plus-rituximab or 
      venetoclax-plus-obinutuzumab. In patients with un-mutated (but not with mutated) 
      IGHV higher PFS proportions and favorable HRs were observed for acalabrutinib, 
      acalabrutinib-plus-obinutuzumab, and ibrutinib-plus-obinutuzumab relative to 
      ibrutinib; and targeted therapies were superior over chemoimmunotherapies in 
      patients with del 17p. Targeted therapies containing ibrutinib or acalabrutinib 
      regimens were associated with superior TTNT over venetoclax-plus-obinutuzumab and 
      all chemoimmunotherapies. OS NMA generally found no difference between therapies 
      except for some chemoimmunotherapies. CONCLUSIONS: Overall, only 
      acalabrutinib-plus-obinutuzumab was associated with superior 5-year PFS gains 
      over ibrutinib, which in turn was similar or superior in PFS benefit over other 
      targeted therapies. Acalabrutinib and ibrutinib with obinutuzumab and 
      acalabrutinib monotherapy were associated with greater 5-year TTNT benefits. 
      Despite marked 5-year OS for many regimens, a differential 5-year OS benefit 
      could not be ascertained.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Alrawashdh, Neda
AU  - Alrawashdh N
AD  - Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 
      Tucson, AZ; Department of Clinical Translational Sciences, College of Medicine, 
      University of Arizona, Tucson, AZ.
FAU - Persky, Daniel O
AU  - Persky DO
AD  - Banner University Medical Center, Tucson, AZ; University of Arizona Cancer 
      Center, Tucson, AZ.
FAU - McBride, Ali
AU  - McBride A
AD  - University of Arizona Cancer Center, Tucson, AZ.
FAU - Sweasy, Joann
AU  - Sweasy J
AD  - University of Arizona Cancer Center, Tucson, AZ.
FAU - Erstad, Brian
AU  - Erstad B
AD  - Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 
      Tucson, AZ; Department of Pharmacy Practice and Science, College of Pharmacy, 
      University of Arizona, Tucson, AZ.
FAU - Abraham, Ivo
AU  - Abraham I
AD  - Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 
      Tucson, AZ; University of Arizona Cancer Center, Tucson, AZ; Department of 
      Pharmacy Practice and Science, College of Pharmacy, University of Arizona, 
      Tucson, AZ. Electronic address: abraham@pharmacy.arizona.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210623
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
SB  - IM
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/*mortality
MH  - Network Meta-Analysis
OTO - NOTNLM
OT  - CLL
OT  - Progression free
OT  - front line
OT  - survival
OT  - targeted therapy
EDAT- 2021/07/19 06:00
MHDA- 2022/02/17 06:00
CRDT- 2021/07/18 20:32
PHST- 2021/05/11 00:00 [received]
PHST- 2021/06/06 00:00 [revised]
PHST- 2021/06/14 00:00 [accepted]
PHST- 2021/07/19 06:00 [pubmed]
PHST- 2022/02/17 06:00 [medline]
PHST- 2021/07/18 20:32 [entrez]
AID - S2152-2650(21)00239-1 [pii]
AID - 10.1016/j.clml.2021.06.010 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):e820-e831. doi: 
      10.1016/j.clml.2021.06.010. Epub 2021 Jun 23.