Photo Credit: Nemes Laszlo

The following is a summary of “Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia,” published in the February 2025 issue of New England Journal of Medicine by R. Brown et al.

Researchers conducted a retrospective study on fixed-duration acalabrutinib–venetoclax (±obinutuzumab) vs chemoimmunotherapy in untreated chronic lymphocytic leukemia (CLL), finding improved progression-free survival (PFS). 

They conducted a phase 3, open-label trial with patients ≥18 years old, ECOG score 0–2, without 17p deletion or TP53 mutation. They randomly assigned patients (1:1:1) to acalabrutinib–venetoclax (cycles 1–14, venetoclax from cycle 3), acalabrutinib–venetoclax–obinutuzumab (as above, plus obinutuzumab, cycles 2–7), or chemoimmunotherapy (fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab, cycles 1–6). They assessed PFS as the primary endpoint by blinded independent central review. 

The results showed that among 867 patients (median age 61, 64.5% men, 58.6% with unmutated IGHV), 36-month PFS was 76.5% with acalabrutinib–venetoclax, 83.1% with acalabrutinib–venetoclax–obinutuzumab, and 66.5% with chemoimmunotherapy (HR 0.65, 95% CI 0.49–0.87, P=0.004; P<0.001 for acalabrutinib–venetoclax–obinutuzumab vs chemoimmunotherapy). Overall survival (OS) was 94.1%, 87.7%, and 85.9%, respectively. Grade ≥3 neutropenia occurred in 32.3%, 46.1%, and 43.2%, and COVID-19 deaths were 10, 25, and 21, respectively. 

Investigators found that acalabrutinib–venetoclax with or without obinutuzumab significantly prolonged PFS compared with chemoimmunotherapy in fit patients with untreated CLL. 

Source: nejm.org/doi/full/10.1056/NEJMoa2409804