Photo Credit: Nemes Laszlo
The following is a summary of “A Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab (AVO) in a Treatment-Naive CLL Population Enriched for High-Risk Disease,” published in the December 2024 issue of Oncology by Davids et al.
The AMPLIFY trial established a fixed-duration regimen of acalabrutinib, venetoclax, and obinutuzumab as the standard of care for patients with treatment-naive chronic lymphocytic leukemia (CLL) with wild-type TP53, excluding patients with TP53 genetic mutations.
Researchers conducted a prospective study to evaluate the safety and efficacy of acalabrutinib, venetoclax, and obinutuzumab in treatment-naive patients with high-risk CLL, especially those with TP53 genetic mutations.
They enrolled 72 patients, including 45 with TP53 genetic mutations, who received acalabrutinib, obinutuzumab, followed by venetoclax in sequence. Treatment duration was determined by measurable residual disease (MRD) levels. Patients who achieved undetectable MRD after 15 or 24 cycles could stop treatment.
The results showed that the complete response rate with bone marrow undetectable MRD (BM-uMRD) at the start of cycle 16 was 42% for patients with TP53 mutations and 42% for all participants. The BM-uMRD rates were 71% for patients with TP53 mutations and 78% for all patients. Hematologic toxicities were mostly mild, with infrequent cardiovascular toxicities and bleeding complications. After a median follow-up of 55.2 months, 10 patients experienced disease progression, including 4 with transformation to a more aggressive form, and 3 patients died, 4-year progression-free survival was 70% for patients with TP53 mutations and 96% for all patients, while 4-year OS was 88% for patients with TP53 mutations and 100% for all patients.
They concluded that acalabrutinib, venetoclax, and obinutuzumab were highly effective and well-tolerated in treatment-naive patients with high-risk CLL, offering a promising new treatment option.
Source: ascopubs.org/doi/10.1200/JCO-24-02503
