Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis
Abstract: Bruton tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), defined based on the presence of genetic mutations. Given the lack of head-to-head trials comparing next-genera...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002162 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331048740028416 |
|---|---|
| author | Mazyar Shadman Jennifer R. Brown Leyla Mohseninejad Keri Yang Heather Burnett Binod Neupane Rhys Williams Nicole Lamanna Susan M. O'Brien Alessandra Tedeschi Constantine S. Tam |
| author_facet | Mazyar Shadman Jennifer R. Brown Leyla Mohseninejad Keri Yang Heather Burnett Binod Neupane Rhys Williams Nicole Lamanna Susan M. O'Brien Alessandra Tedeschi Constantine S. Tam |
| author_sort | Mazyar Shadman |
| collection | DOAJ |
| description | Abstract: Bruton tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), defined based on the presence of genetic mutations. Given the lack of head-to-head trials comparing next-generation BTKis used to treat high-risk R/R disease, a network meta-analysis (NMA) was performed to estimate their relative efficacy. High-risk populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE (n = 150) and ASCEND (n = 86) trials, and del(17p)/del(11q) in the ELEVATE-RR (n = 533) trial. Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [HR], 0.49; 95% credible interval [CrI], 0.31-0.78), acalabrutinib (HR, 0.55; 95% CrI, 0.32-0.94), and bendamustine + rituximab or idelalisib + rituximab (BR/IR; HR, 0.12; 95% CrI, 0.05-0.26). Differences in overall survival demonstrated a numerical trend favoring zanubrutinib (probability better than ≥80%) compared with ibrutinib (HR, 0.59; 95% CrI, 0.31-1.11), acalabrutinib (HR, 0.72; 95% CrI, 0.35-1.50), and BR/IR (HR, 0.65; 95% CrI, 0.23-1.75). Rates of response also demonstrated trends favoring zanubrutinib compared with acalabrutinib, with significant results compared with ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib. |
| format | Article |
| id | doaj-art-ee2620bcdd8942b4b7bfa0785cf1960f |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-ee2620bcdd8942b4b7bfa0785cf1960f2025-08-20T03:46:45ZengElsevierBlood Advances2473-95292025-06-019122863287010.1182/bloodadvances.2024014523Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysisMazyar Shadman0Jennifer R. Brown1Leyla Mohseninejad2Keri Yang3Heather Burnett4Binod Neupane5Rhys Williams6Nicole Lamanna7Susan M. O'Brien8Alessandra Tedeschi9Constantine S. Tam10Clinical Research Division, Fred Hutchinson Cancer Center and Hematology and Oncology Division, University of Washington, Seattle, WA; Correspondence: Mazyar Shadman, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M2-B861, Seattle, WA 98109;Chronic Lymphocytic Leukemia Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MABeOne Medicines Ltd, Schiphol, The NetherlandsBeOne Medicines Ltd, San Mateo, CAEvidera, Montreal, CanadaEvidera, Montreal, CanadaBeOne Medicines Ltd, San Mateo, CAHematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NYDivision of Hematology/Oncology, School of Medicine, University of California, Irvine, CADepartment of Hematology, Azienda Socio Sanitaria Grande Ospedale Metropolitano Niguarda, Milan, ItalyLymphoma Service, Alfred Hospital and Monash University, Melbourne, Victoria, AustraliaAbstract: Bruton tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), defined based on the presence of genetic mutations. Given the lack of head-to-head trials comparing next-generation BTKis used to treat high-risk R/R disease, a network meta-analysis (NMA) was performed to estimate their relative efficacy. High-risk populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE (n = 150) and ASCEND (n = 86) trials, and del(17p)/del(11q) in the ELEVATE-RR (n = 533) trial. Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [HR], 0.49; 95% credible interval [CrI], 0.31-0.78), acalabrutinib (HR, 0.55; 95% CrI, 0.32-0.94), and bendamustine + rituximab or idelalisib + rituximab (BR/IR; HR, 0.12; 95% CrI, 0.05-0.26). Differences in overall survival demonstrated a numerical trend favoring zanubrutinib (probability better than ≥80%) compared with ibrutinib (HR, 0.59; 95% CrI, 0.31-1.11), acalabrutinib (HR, 0.72; 95% CrI, 0.35-1.50), and BR/IR (HR, 0.65; 95% CrI, 0.23-1.75). Rates of response also demonstrated trends favoring zanubrutinib compared with acalabrutinib, with significant results compared with ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib.http://www.sciencedirect.com/science/article/pii/S2473952925002162 |
| spellingShingle | Mazyar Shadman Jennifer R. Brown Leyla Mohseninejad Keri Yang Heather Burnett Binod Neupane Rhys Williams Nicole Lamanna Susan M. O'Brien Alessandra Tedeschi Constantine S. Tam Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis Blood Advances |
| title | Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis |
| title_full | Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis |
| title_fullStr | Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis |
| title_full_unstemmed | Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis |
| title_short | Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis |
| title_sort | comparative efficacy of bruton tyrosine kinase inhibitors in high risk relapsed refractory cll a network meta analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002162 |
| work_keys_str_mv | AT mazyarshadman comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT jenniferrbrown comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT leylamohseninejad comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT keriyang comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT heatherburnett comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT binodneupane comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT rhyswilliams comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT nicolelamanna comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT susanmobrien comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT alessandratedeschi comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis AT constantinestam comparativeefficacyofbrutontyrosinekinaseinhibitorsinhighriskrelapsedrefractorycllanetworkmetaanalysis |