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.
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.”
- 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).