ArticleHemaSphere2026
A functional prognostic model predicts progression-free survival in patients with relapsed chronic lymphocytic leukemia treated with ibrutinib + venetoclax.
Article in HemaSphere, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03226301 (A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia), which is not on this map. Not yet cited in PubMed.
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A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations
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25 authors.
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Abstract
Targeted therapies have improved outcomes for patients with chronic lymphocytic leukemia (CLL); yet, not all achieve durable responses. Existing prognostic models, developed for chemoimmunotherapy, have limited predictive value for newer targeted combinations. Here, we used data from a randomized phase II clinical trial to identify predictors of progression-free survival (PFS) in response to Bruton tyrosine kinase (BTK) + B-cell lymphoma 2 (Bcl-2) inhibitor combination therapy. We studied the functional, genetic, and clinical characteristics of patients with relapsed/refractory (R/R) CLL treated with ibrutinib + venetoclax in the VISION/HO141 clinical trial (NCT03226301). Ex vivo drug sensitivity testing, (phospho)protein profiling, and immunophenotyping were performed on baseline peripheral blood mononuclear cells from 177 patients. Ex vivo drug sensitivity correlated with clinical responses to single-agent therapies. (Phospho)protein patterns reflected intracellular pathway activity and predicted ex vivo drug sensitivity. Using stringent feature selection and regularized ridge regression to prevent overfitting, we integrated functional, genetic, and clinical data sets and identified six features-sensitivity to VEGFR-2-, JAK1/2 + Bcl-2-, and BTK + PI3K-inhibitors; phosphorylation ratios of Bcl-2:BTK and p90RSK:PLCγ2; and frequency of CD8
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