Real-world evidence on venetoclax in chronic lymphocytic leukemia: The Italian experience

Abstract

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the western world. In Italy, venetoclax was approved for use in patients with CLL as monotherapy in 2017 and in combinations in 2019. As a result of this delayed approval, there are relatively few real-world studies from Italian clinical practice and much of the data are in heavily pretreated patients. We have collected the available studies in Italian routine practice. Three studies confirm the effectiveness and tolerability of this agent in patients with relapsed/refractory CLL and high-risk disease characteristics, many of whom had received prior B-cell receptor signaling treatment. Addition of rituximab to venetoclax produced more complete responses in patients with relapsed/refractory CLL, while higher disease burden and progression while receiving a prior Bruton's tyrosine kinase inhibitor were both associated with poorer outcomes in patients treated with venetoclax. Venetoclax was well-tolerated with low discontinuation rates. No studies of venetoclax plus obinutuzumab for the first-line treatment of patients with CLL were available due to the short time since approval in Italy. Several cohorts addressed the impact of COVID-19 on patient management and outcomes, suggesting that treated patients and those in clinical observation had similar rates of COVID-19-related hospital admission, intensive care unit admission, and mortality. Overall, the responses and tolerance to venetoclax observed in the Italian real-world setting confirm the tolerability and effectiveness of venetoclax regimens in high-risk patients.

Keywords: B-cell; Bcl-2; Italy; chronic; leukemia; lymphocytic; real-world evidence; venetoclax.