Comparison between Time- - PowerPoint Presentation

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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

Targeted

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

Quality 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

Results: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

Results:

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

Results:

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

Results:

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

Results:

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

Conclusions

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