Safety and efficacy of venetoclax–rituximab protocol after BTK inhibitor treatment in a patient with chronic lymphocytic leukemia

Abstract

Venetoclax, a BCL-2 inhibitor, in combination with rituximab, is effective in the treatment of chronic lymphocytic leukemia (CLL), both with and without del(17p) or TP53 mutation. In the manuscript, we present a case of a 50-year-old woman who was diagnosed with CLL at the age of 34 years. She had been receiving many different protocols of chemoimmunotherapy, including fludarabine. Recently, she had been treated with Bruton’s tyrosine kinase inhibitor — ibrutinib. After 52 months of response to ibrutinib she developed progression of CLL with accompanying general symptoms and clonal evolution — a new del(17p). The patient was qualified to receive venetoclax for 2 years continuously counted from day 1 cycle 1 at a dose of 400 mg, after previous 5-week gradual dose increase, and rituximab for the first 6 months of treatment.

The first dose ramp-up of venetoclax was interrupted at a dose of 50 mg per day because of fever and grade 3 neutropenia. After Richter transformation and infection had been excluded, the second ramp-up of venetoclax was conducted along with granulocyte colony-stimulating factor (G-CSF) and antipyretics. This time the target dose of venetoclax was achieved without complications and rituximab was initiated. As a result of treatment, lymphadenopathy and general symptoms resolved and complete blood count parameters improved significantly. The patient continues the therapy.

To conclude, the combination venetoclax-rituximab is effective, also in heavily pretreated patients, and patients with del(17p). Response to treatment is rapid. Adverse events may occur, especially during the early phase of treatment, e.g. neutropenia. It may be necessary to administer concurrently G-CSF in order to achieve target dose of venetoclax on schedule.