AMPLIFY (acalabrutinib/venetoclax/obinutuzumab)
Trial question
What is the effect of acalabrutinib/venetoclax/obinutuzumab in patients with previously untreated chronic lymphocytic leukemia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
34.0% female
66.0% male
N = 576
576 patients (195 female, 381 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=286 acalabrutinib/venetoclax/obinutuzumab (acalabrutinib 100 mg BID during cycles 1-14 and venetoclax once daily during cycles 3-14 plus intravenous obinutuzumab 1,000 mg during cycles 2-7).
N=290 chemoimmunotherapy (intravenous fludarabine/cyclophosphamide/rituximab or bendamustine/rituximab during cycles 1-6 according to standard dosing protocols).
Primary outcome
Progression-free survival at 36 months
83.1%
66.5%
83.1 %
62.3 %
41.5 %
20.8 %
0.0 %
Acalabrutinib/venetoclax/obinutuzumab
Chemoimmunotherapy
Significant
increase ▲
NNT = 6
Significant increase in progression-free survival at 36 months (83.1% vs. 66.5%; AD 16.6%, 95% CI 6.75 to 26.45).
Secondary outcomes
No significant difference in overall survival at 36 months (87.7% vs. 85.9%; HR 1.32, 95% CI 0.85 to 2.04).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with previously untreated chronic lymphocytic leukemia, acalabrutinib/venetoclax/obinutuzumab was superior to chemoimmunotherapy with respect to a 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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