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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Network meta-analysis of novel targeted therapies for relapsed/refractory chronic lymphocytic leukemia
Magdalena Monica1,2, Monika Reczek3, Paweł Kawalec2
1Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Łazarza 16, Kraków 31-530, Poland.
Background:
The recent development of new antileukemic therapies (anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhbitors, phosphoinositide 3-kinase inhibitors, and B-cell lymyphoma-2 antagonists) improved the progression-free survival (PFS) compared with selected standard regimens in clinical trials for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Unfortunately, the relative efficacy of all possible therapeutic options remains unknown because there is no direct evidence for all possible comparisons.
Objectives:
We aimed to compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy using a Bayesian network meta-analysis (NMA).
Design:
Systematic literature review with Bayesian NMA.
Methods:
An extensive systematic literature review of randomized clinical trials for relapsed/refractory CLL was performed. We searched for articles indexed in medical databases (MEDLINE, Embase, The Cochrane Library) and gray literature that could be further implemented into the Bayesian NMA.
Results:
The systematic search identified 15 randomized trials that formed networks comparing PFS, overall survival (OS), overall response rates, and serious adverse events. Our study showed that all regimens containing novel agents significantly prolonged PFS compared with standard chemoimmunotherapy and immunotherapy. Among targeted drugs, venetoclax (VEN) + rituximab (RTX) had comparable efficacy in terms of PFS to zanubrutinib (ZAN) [hazard ratio (95% credible interval), 1.10 (0.59-2.08)], acalabrutinib (ACA) [0.78 (0.47-1.30)], ibrutinib (IBR) monotherapy [0.72 (0.41-1.27)], and other IBR-based regimens. ZAN was superior to IBR monotherapy [0.65 (0.49-0.86)] but not to ACA [0.71 (0.49-1.02)]. There were no significant differences in OS in any of the above comparisons.
Conclusion:
All novel therapies have better efficacy than chemoimmunotherapy and immunotherapy regimens. Among novel agents, the relative efficacy of VEN + RTX was similar to all BTKi, while ZAN was superior to IBR and comparable to ACA.
Trial Registration:
PROSPERO CRD42022304330.
Insights
Novel therapies significantly improve progression-free survival (PFS) in relapsed/refractory chronic lymphocytic leukemia (CLL) compared to standard treatments. Venetoclax plus rituximab showed similar PFS to Bruton tyrosine kinase inhibitors (BTKIs), while zanubrutinib outperformed ibrutinib.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Relapsed/refractory chronic lymphocytic leukemia (CLL) presents treatment challenges.
- Recent advancements include novel agents like anti-CD20 antibodies, BTK inhibitors, PI3K inhibitors, and BCL-2 antagonists.
- Direct comparative efficacy data for all therapeutic options is lacking.
Purpose of the Study:
- To compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy in relapsed/refractory CLL.
- To utilize a Bayesian network meta-analysis (NMA) for direct and indirect treatment comparisons.
Main Methods:
- Systematic literature review of randomized clinical trials (RCTs) for relapsed/refractory CLL.
- Inclusion of studies from MEDLINE, Embase, The Cochrane Library, and gray literature.
- Bayesian network meta-analysis (NMA) to synthesize data from 15 RCTs.
Main Results:
- All novel agent regimens significantly prolonged progression-free survival (PFS) versus standard chemoimmunotherapy and immunotherapy.
- Venetoclax (VEN) + rituximab (RTX) demonstrated comparable PFS to zanubrutinib (ZAN), acalabrutinib (ACA), and ibrutinib (IBR)-based regimens.
- Zanubrutinib (ZAN) showed superior PFS compared to ibrutinib (IBR) monotherapy but was comparable to acalabrutinib (ACA).
Conclusions:
- Novel therapies offer superior efficacy compared to chemoimmunotherapy and immunotherapy for relapsed/refractory CLL.
- Among novel agents, VEN+RTX showed similar PFS to all Bruton tyrosine kinase inhibitors (BTKIs).
- Zanubrutinib (ZAN) demonstrated superior efficacy over ibrutinib (IBR) and comparable efficacy to acalabrutinib (ACA).
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