ArticleCancer medicine2026
Acalabrutinib Versus Venetoclax Plus Obinutuzumab in Treatment-Naive Chronic Lymphocytic Leukemia: A Real-World Propensity Score-Matched Study.
Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTherapy for chronic lymphocytic leukemia (CLL) has shifted from chemoimmunotherapy to targeted agents such as Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. Approved first-line options include acalabrutinib, a second-generation BTK inhibitor, and the fixed-duration combination venetoclax-obinutuzumab, yet real-world head-to-head data are scarce.
methodsUsing the TriNetX global federated health database, we retrospectively compared outcomes in treatment-naïve patients with TP53-unmutated CLL who received either regimen as initial therapy. After applying eligibility criteria and 1:1 propensity score matching, 669 matched pairs were analyzed. The primary endpoint was time to next treatment (TTNT); secondary endpoints included overall survival (OS) and adverse events.
resultsThe results showed that patients treated with venetoclax plus obinutuzumab had a significantly longer TTNT (median not reached vs. 47.7 months) and improved 4-year OS. Across all subgroups, the venetoclax-based regimen performed better. Cytopenias and infections were more common with venetoclax-obinutuzumab-neutropenia 54.3% versus 33.3%, thrombocytopenia 45.9% versus 31.9%, febrile neutropenia 7.1% versus 3.4%, and tumor lysis syndrome 6.3% versus 2.3%. Acalabrutinib caused fewer severe hematologic toxicities.
conclusionIn real-world practice, venetoclax plus obinutuzumab was associated with longer TTNT and improved OS compared to acalabrutinib as first-line therapy in patients with TP53 wild-type CLL.
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