Continuous venetoclax in treatment-naive TP53 disrupted patients with chronic lymphocytic leukemia: A chronic lymphocytic leukemia campus study

Deletion of 17p13 (17p-) and/or TP53 gene mutation (TP53m), collectively defined as TP53 abnormalities (TP53 abn), can be found in 8 to 10% of treatment-naive (TN) patients with chronic lymphocytic leukemia (CLL) and in up to 50% of relapsed/refractory cases.1 In CLL TP53 disruption is a negative prognostic and predictive biomarker, associated with shorter time to first treatment, karyotype complexity, Richter transformation as well as shorter survival.2, 3 In addition, this adverse genetic feature has been associated with an increased risk of treatment failure in patients treated with continuous BTK inhibitors (BTKi).4, 5 Fixed duration venetoclax-based therapy, in combination with anti-CD20 monoclonal antibody, is a highly active treatment for TN and relapsed/refractory patients with CLL.6, 7 However, patients with TP53 abnormalities display shorter measurable residual disease (MRD) doubling time and early relapse after the end of treatment.6, 7 Continuous treatment with BTKi is a valid option in TP53 disrupted patients, counteracted by a relatively high rate of discontinuation due to adverse events,8, 9 beside second-generation BTK are better tolerated than ibrutinib. In the phase II study investigating venetoclax in TP53-disrupted patients with CLL, only five patients were TN, and 4/5 were remission-free after a median follow-up of 2 years.10 The aim of this study is to describe the efficacy and discontinuation rate of continuous venetoclax in TN CLL patients with TP53 disruption.