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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Monday, February 10, 2025
Fixed-duration acalabrutinib, venetoclax, and obinutuzumab (AVO) may be an effective treatment option—potentially even a new standard-of-care option—in patients with previously untreated chronic lymphocytic leukemia (CLL) who have the high-risk TP53 aberration, according to results of the multicenter phase II AMPLIFY trial published in the Journal of Clinical Oncology. The combination of the Bruton’s tyrosine kinase inhibitor, the BCL2 inhibitor, and the monoclonal antibody had not previously been evaluated in patients with CLL and this aberration, noted Matthew S. Davids, MD, MMSc, of Dana-Farber Cancer Institute, Boston, and colleagues. (See a video with Dr. Davids on this triplet regimen for TP53-aberrant CLL.)
A total of 72 patients with treatment-naive CLL were accrued for this study, 45 of whom had a TP53 aberration. The patients received acalabrutinib, obinutuzumab, and then venetoclax, with each treatment introduced sequentially and in combination, with the duration guided by measurable residual disease (MRD). “The primary endpoint was complete remission with undetectable bone marrow MRD at the start of cycle 16,” they noted.
AVO was active and well tolerated, reported the team, with most hematologic toxicities of low grade; cardiovascular toxicities and bleeding complications were infrequent. As for the endpoint, “the complete remission rate with undetectable bone marrow MRD rate at the start of cycle 16 was 42% in patients with TP53 aberration and 42% in all-comers, and the undetectable bone marrow MRD rates were 71% and 78%, respectively,” stated Dr. Davids and co-researchers. Further, the 4-year progression-free survival rates for patients with or without TP53 aberration were 70% and 96%, respectively; for overall survival, they were respectively 88% and 100%.
An MRD-guided approach individualizes therapy duration, said the authors. “This may be particularly helpful for those patients with high genetic risk who may benefit from a longer therapy duration,” they continued. Future randomized studies should confirm whether the AVO regimen offers superior efficacy over the current standards in the TP53-aberrant population.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
