LimitedVenetoclax Based and Continuous Bruton Thyrosine Kinase InhibitorsBased Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia CLLa Systematic Review and Network MetaAnalysis ID: 930356
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Slide1
Comparison between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-Analysis
Stefano Molica, MD1, Diana Giannarelli, PhD2 and Emili Montserrat, MD31Dipartimento Onco-Ematologico, Azienda Ospedaliera Pugliese - Ciaccio, Catanzaro, Italy2Bio-statistical Unit, Regina Elena National Cancer Institute IRCCS, Rome, Italy3Department of Hematology, Hospital Clinic, University of Barcelona, Barcelona, Spain, Barcelona, Spain subhead
CLL:
Therapy
,
excluding
Transplantation
: Poster III;
Publication
Number
: 3152
Slide2Slide3Targeted
agents (TAs) have shown impressive activity in the upfront treatment of chronic lymphocytic leukemia (CLL).
TAs
have
rarely been compared in head-to-head clinical trialsA systematic literature review and network meta-analysis (NMA) was performed to estimate the relative efficacy and safety of TAs approved bythe FDA and/or EMA for upfront therapy of CLL (i.e., ibrutinib, acalabrutinib, and venetoclax).
Licensed byFDA EMA
Comparison
between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation: Poster III; Publication Number: 3152
/
Background
Slide4Quality of studies assessed according to Cochrane Handbook for Systematic Reviews of Interventions,
ILLUMINATE
Comparison
between
Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based
Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-AnalysisCLL: Therapy, excluding
Transplantation: Poster III; Publication Number: 3152
Methods
:PRISMA Flow Diagram for the Systematic Review and Meta-analysis.N=1191 pts
Slide5Results:Characteristics of
patients enrolled in the ILLUMINATE, CLL14 and ELEVATE-TN trial.
Study
Experimental armMedian time of exposition to targeted agent (mo.) Median age of pts.Median follow-up(mo)Pts. with CIRS* score > 6Pts. with unmutated IGHV
Pts. with TP53 aberrationsPts. with 11q deletion
ILLUMINATEIbrutinib+
Obinutuzumab29.3
71 years31.332.7%62%12%12%CLL14Venetoclax +
Obinutuzumab11.1
70
years
28.3
86.1%
66.5%
10.6%
12%
ELEVATE-TN
Acalabrutinib
27.7
72
years
28.1
11.7%60%11%18%ELEVATE-TNAcalabrutinib + Obinutuzumab27.770 years28.316.8% 57.5%11.7%17.3%
Comparison
between
Time-
Limited,Venetoclax
-
Based
and
Continuous
Bruton
Thyrosine
Kinase
Inhibitors-Based
Therapy
in the
Upfront
Treatment of
Chronic
Lymphocytic
Leukemia
(CLL):a
Systematic
Review
and Network Meta-Analysis
CLL:
Therapy
,
excluding
Transplantation
: Poster III;
Publication
Number
: 3152
Slide6Results:
NMA comparing PFS between ibrutinib-obinutuzumab (IO)(ILLUMINATE), venetoclax-obinutuzumab (VO)(CLL14) and acalabrutinb-obinutuzumab (AO) (ELEVATE-TN trial).
Comparison
between
Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation: Poster III; Publication Number: 3152
Slide7Results:
NMA comparing PFS between ibrutinib-
obinutuzumab
(IO)
(ILLUMINATE), venetoclax-obinutuzumab (VO)(CLL14) and acalabrutinb single agent (A) (ELEVATE-TN trial).Comparison between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic
Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation: Poster III; Publication Number: 3152
A
A
Slide8Results:
NMA comparing AEs (G 3-4) between ibrutinib-
obinutuzumab
(IO)
(ILLUMINATE), venetoclax-obinutuzumab (VO)(CLL14) and acalabrutinb single agent (A) (ELEVATE-TN trial).Comparison between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a
Systematic Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation: Poster III; Publication Number: 3152
*)
*)
*) Results were similar when comparison was performed with acalabrutinib/obinutuzumab arm of ELEVATE-TN trial.AA
Slide9Results:
NMA comparing PFS between ibrutinib-
obinutuzumab
(IO)
(ILLUMINATE), venetoclax-obinutuzumab (VO)(CLL14) and acalabrutinb single agent (A) (ELEVATE-TN trial) with TP53 aberrations.*) Results were similar when comparison was performed with acalabrutinib/obinutuzumab arm of ELEVATE-TN trial.
**
Comparison between Time-Limited,Venetoclax
-Based and Continuous Bruton Thyrosine Kinase
Inhibitors-Based Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation: Poster III; Publication Number: 3152AA
Slide10Conclusions
NMA including the ILLUMINATE, ELEVATE-TN, and CLL14 trials does not reveal significant difference in terms of PFS between time limited (VO) and continuous therapy (IO, A ).In contrast, AO improved PFS in comparison
to IO and VO.
Patients
bearing TP53 aberrations experienced a similar PFS whathever the TA used (i.e., ibrutinib, acalabrutinib, and venetoclax). The rate of AEs (G 3-4) was similar with ibrutibinib, acalabrutinib and venetoclax.Ongoing studies will further delineate the position of different TAs and schedule of administration in CLL therapy based on effectiveness, availability, safety, cost, treatment objectives, and patient choice.
Comparison between Time-Limited,Venetoclax-Based and Continuous Bruton Thyrosine Kinase Inhibitors-Based
Therapy in the Upfront Treatment of Chronic Lymphocytic Leukemia (CLL):a Systematic
Review and Network Meta-AnalysisCLL: Therapy, excluding Transplantation
: Poster III; Publication Number: 3152