Venetoclax monotherapy demonstrated promising activity and an acceptable safety profile in patients with chronic lymphocytic leukemia who are relapsed/refractory to ibrutinib or idelalisib, a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting has shown.1

Patients with CLL who relapse after or become refractory to B-cell receptor (BCR) pathway inhibitors have poor outcomes. Venetoclax is a selective, oral B-cell lymphoma 2 (BCL-2) inhibitor approved for use in patients with CLL and 17p deletion, each of whom received at least 1 prior therapy. Researchers examined treatment outcomes with ibrutinib in patients relapsed/refractory to ibrutinib or idelalisib.

For the phase 2 trial, investigators enrolled 38 patients with CLL relapsed/refractory to ibrutinib and 10 patients relapsed/refractory to idelalisib. More than half (54%) had received greater than 5 prior therapies, 83% had unmutated IGHV, 35% had del17p, and 24% had at least 1 node ≥10 cm. All participants received venetoclax 20 mg daily followed by a 5-week increase to 400 mg daily.

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It was found that the overall response rate was 61% in ibrutinib pre-treated patients and 50% in those who previously received idelalisib, with 3 patients in the ibrutinib arm achieving a complete response. Eight patients who previously received ibrutinib had minimal residual disease negativity by flow cytometry in blood at 24 weeks.

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Results showed that the venetoclax safety profile was consistent with previous reports. The most common adverse events were neutropenia (48%), diarrhea (37%), nausea (35%), anemia (32%), fatigue (24%), hyperphosphatemia (20%). The most frequently reported grade 3 to 4 adverse events included neutropenia (39%), thrombocytopenia (22%), anemia (20%), leukopenia (13%), pneumonia (13%).

“This is the first prospective study to demonstrate efficacy in this poor-prognosis population,” the authors conclude. “Follow-up will assess depth and duration of response.”                                      


  1. Jones JA, Wierda WG, Choi MY, Davids MS, Cheson BD, Furman RR, et al. Venetoclax activity in CLL patients who have relapsed after or are refractory to ibrutinib or idelalisib. J Clin Oncol. 2016; 34 (suppl; abstr 7519).