AMPLIFY Study: Upfront Acalabrutinib-Based Combo Effective in High-Risk CLL

The AMPLIFY trial evaluated whether a new first-line treatment is more effective than the standard of care as a frontline treatment for patients with chronic lymphocytic leukemia (CLL) but did not include patients with the TP53 aberration. A later phase 2 AMPLIFY study evaluated whether the combination of acalabrutinib, venetoclax, and obinutuzumab (AVO) was safe and effective as first-line treatment for patients with CLL who had the TP53 aberration. People with the TP53 aberration have the TP53 mutation and/or 17p deletion, which is an important predictive marker in CLL, according to the NIH.

Patients received AVO for as long as measurable residual disease (MRD) was detected. Patients who had undetectable MRD (uMRD) after 15 or 24 cycles were able to stop treatment. The primary end point was complete remission (CR) with bone marrow uMRD at the beginning of cycle 16.

Investigators enrolled 72 patients from Dana-Farber Cancer Institute (DFCI), Beth Israel Deaconess Medical Center (both in Boston), Brown University Health (Providence, RI), and Stamford Hospital (Stamford, CT). Of those, 45 patients had the TP53 aberration. At the start of cycle 16, 42% of patients with the TP53 aberration (and 42% of the other patients receiving the treatment) experienced CR with bone marrow uMRD. The findings were published in the Journal of Clinical Oncology, authored by Matthew S. Davids, MD, MMSc, of DFCI, and colleagues.

Hematologic and cardiovascular toxicities occurred in a few patients, and bleeding complications were rare. After a median follow-up of 55.2 months, 10 patients had disease progression and three died. Four-year progression-free survival was 70% for those who had the aberration and 96% for those without. Overall survival for patients with and without the TP53 aberration was 88% and 100%, respectively. Based on the early promising results, the investigators enrolled 35 more patients with the TP53 aberration in the trial.

The investigators concluded that AVO may be a new option for treatment-naive patients with high-risk CLL.

The authors later provided a correction, “When reviewing available patient samples in this trial for a future laboratory study, the authors discovered that the samples that were sent for ClonoSEQ MRD analysis for this study were derived from the patients’ bone marrow (BM), not peripheral blood (PB), as is currently written in the online form of the article. Although this does not have a substantive effect on the outcome of the study, the authors would like to make this correction to ensure the paper is accurate.”