AMPLIFY (acalabrutinib/venetoclax)
Trial question
What is the effect of acalabrutinib/venetoclax in patients with previously untreated chronic lymphocytic leukemia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 581
581 patients (220 female, 361 male).
Inclusion criteria: patients with previously untreated chronic lymphocytic leukemia.
Key exclusion criteria: prior chronic lymphocytic leukemia-specific therapies; detected del(17p) or TP53 mutation; transformation of chronic lymphocytic leukemia to aggressive non-Hodgkin's lymphoma, prolymphocytic leukemia, or diffuse large B-cell lymphoma, or CNS involvement by leukemia; confirmed progressive multifocal leukoencephalopathy; receipt of investigational drug within 30 days before the first dose of study drug; major surgical procedure within 30 days before the first dose of study drug.
Interventions
N=291 acalabrutinib/venetoclax (acalabrutinib 100 mg BID during cycles 1-14 and venetoclax once daily during cycles 3-14).
N=290 chemoimmunotherapy (intravenous fludarabine/cyclophosphamide/rituximab or bendamustine/rituximab during cycles 1-6 according to standard dosing protocols).
Primary outcome
Median progression-free survival at 36 months
76.5%
66.5%
76.5 %
57.4 %
38.3 %
19.1 %
0.0 %
Acalabrutinib/venetoclax
Chemoimmunotherapy
Significant
increase ▲
NNT = 10
Significant increase in median progression-free survival at 36 months (76.5% vs. 66.5%; HR 1.54, 95% CI 1.15 to 2.04).
Secondary outcomes
Significant increase in overall survival at 36 months (94.1% vs. 85.9%; HR 3.03, 95% CI 1.79 to 5.56).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with previously untreated chronic lymphocytic leukemia, acalabrutinib/venetoclax was superior to chemoimmunotherapy with respect to median progression-free survival at 36 months.
Reference
Jennifer R Brown, John F Seymour, Wojciech Jurczak et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762.
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