Venetoclax Resulted in High Efficacy in Patients With CLL With TP53 Disruption

A research paper presented by Andrea Visentin, MD, PhD, of the University of Padova in Italy, and colleagues at the 64th American Society of Hematology Annual Meeting and Exhibition found a high efficacy of venetoclax in patients with treatment-naïve (TN) chronic lymphocytic leukemia with TP53 disruption.

Fixed-duration venetoclax-based therapy has been documented as a highly active frontline treatment in patients with CLL; however, the researchers noted that “patients with TP53 abnormalities may early relapse after the end of treatment.” The purpose of this study was to evaluate the efficacy and discontinuation rate of continuous venetoclax in patients with TN CLL with TP53 disruption in the real-life setting.

Using medical charts of patients with CLL from 16 centers, 34 patients with TN CLL with TP53 abnormalities were retrospectively identified. The main outcome measurement was the rate of treatment discontinuation, and secondary outcome measurements included overall response rate (ORR), measurable residual disease (MRD) by flow cytometry, progression-free survival (PFS), and overall survival. A cohort of 100 TN patients treated with ibrutinib were identified for comparison.

The best ORR was 85%, which included 50% complete responses (CR) and 35% partial responses. MRD was assessed in the peripheral blood of 14 patients. A total of 6 patients achieved undetectable MRD4, 6 patients had detectable MRD4, and the remaining 2 patients had detectable MRD2. At the mean follow-up period of 20 months, 9 patients decreased the venetoclax dose and 3 discontinued therapy. The median PFS at 12 and 24 months was 96% and 83%, respectively.

When compared with patients being treated with ibrutinib, patients receiving venetoclax had a higher CR rate (50% vs 9%), longer PFS, and lower incidence of discontinuation after 24 months (14% vs 35%).

“To our knowledge, we report the largest real-life study of continuous venetoclax in TN CLL patients with TP53 abnormalities, not previously studied systematically in clinical trials,” the researchers wrote. “Only 1 patient discontinued venetoclax due to toxicity. The use of continuous venetoclax in TN CLL patients with TP53 disruption deserves further investigation, as it can be an effective alternative option besides [a Bruton’s tyrosine kinase] inhibitor.”

Source: Visentin A, Mauro F, Scarfo L, et al. Continuous venetoclax in previously untreated patients with chronic lymphocytic leukemia and TP53 abnormalities. A study of the Italian Campus CLL. Abstract #3131. Presented at the 64th ASH Annual Meeting and Exposition; December 11, 2022; New Orleans, Louisiana.