Many patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who were treated with venetoclax plus rituximab achieved an overall response, including half who achieved a complete response, according to a study published in The Lancet Oncology.1

Selective inhibition of BCL2 with venetoclax has demonstrated substantial activity in patients with relapsed or refractory CLL. Preclinical models suggest that combination therapy with rituximab may enhance activity of venetoclax; researchers therefore evaluated the activity and safety of venetoclax in combination with rituximab in relapsed or refractory CLL.

For the multicenter, open-label, phase 1b, dose-escalation trial (ClinicalTrials.gov Identifier: NCT01682616), researchers enrolled 49 adult patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL). Participants received oral venetoclax daily at a dose of 200 to 600 mg and intravenous rituximab monthly for 6 months.

Results showed that 86% of the 49 patients achieved a response, including 51% who achieved a complete response. Investigators estimated that 89% (95% CI, 72-96) and 82% (95% CI, 66-91) of patients would be in ongoing response and progression-free at 2 years, respectively.

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Researchers also found that 80% of the 25 complete responders and 57% of the overall sample achieved negative marrow minimal residual disease.

All 11 responders with minimal residual disease negativity remain progression-free after discontinuing therapy. Two patients with minimal residual disease positivity who achieved a complete response progressed after 2 years off therapy, but re-attained response after re-initiating venetoclax.

Investigators recommended venetoclax 400 mg for assessment in combination with rituximab in a phase 2 trial. About 75% of patients experienced grade 3 to 4 adverse events, with the most common being neutropenia, thrombocytopenia, anemia, febrile neutropenia, and leukopenia.

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With results showing the depth and durability of responses with venetoclax plus rituximab, the findings suggest that this combination is an attractive potential treatment option for patients with relapsed or refractory CLL and warrants further investigation in randomized clinical trials.

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