Venetoclax has a favorable safety profile and durable clinical effect among patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) that has progressed during or after ibrutinib therapy, according to a study published in Lancet Oncology.

The prognosis for patients with CLL has markedly improved with the tyrosine kinase inhibitor ibrutinib; nearly 90% of patients achieve a complete response (CR) or partial response (PR) to ibrutinib after 5 years. Unfortunately, patients who relapse or become refractory to ibrutinib have very poor outcomes. Venetoclax monotherapy may be effective in R/R CLL.

For this open-label phase 2 study, researchers treated 91 patients with R/R CLL who had previously failed ibrutinib therapy; 43 patients were initially enrolled into the main cohort and 48 patients were recruited additionally upon protocol amendment into an expansion cohort. All patients were screened for Richter’s transformation, and patients with confirmed cases were not eligible for the study.

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Study participants received venetoclax 20 mg/day that was increased over the course of 5 weeks to 400 mg/day.

The median follow-up at the time of this interim analysis was 14 months. Fifty-nine patients (65%) achieved an investigator-assessed overall response (30 [70%] from the main cohort and 29 [60%] from the expansion cohort).

The most frequently reported grade 3 to 4 adverse events were neutropenia, thrombocytopenia, anemia, leukopenia, and lymphocytopenia. Seventeen patients died during the study; 7 because of disease progression. No deaths were found to be treatment related.

Data from this interim analysis show that venetoclax has clinical effect against R/R CLL that is ibrutinib resistant, which is an important advancement in the management of this patient population. The authors concluded that “continued investigation of treatment in patients with disease while on or progression after BCR inhibitor therapy is crucial to advance the treatment of chronic lymphocytic leukemia.”


Jones JA, Mato AR, Wierda WG, et al. Venetoclax for chronic lymphocytic leukemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial [published online December 12, 2017]. Lancet Oncol. doi: 10.1016/S1470-2045(17)30909-9