Venetoclax monotherapy was active, and even elicited minimal residual disease negativity in a proportion of patients with chronic lymphocytic leukemia (CLL) that was resistant or refractory to ibrutinib or idelalisib, Dr. Jeffrey Alan Jones of the Ohio State University Comprehensive Cancer Center, Columbus, and colleagues wrote in an abstract to be presented at the annual meeting of the American Society of Clinical Oncology.

The findings from their ongoing phase II study are the first prospective results to demonstrate efficacy in this poor-prognosis population, the researchers wrote. Earlier results from the study were reported at the American Society of Hematology meeting.

The 54 patients in the study, 25 of them refractory to ibrutinib and 6 to idelalisib, received venetoclax 20 mg daily followed by a 5-week ramp up in dosage to 400 mg daily. Over half of the patients had received more than five prior therapies; 83% did not have IGHV mutations, 20% had absolute lymphocyte counts exceeding 100 x 109, 35% had 17p deletions, and 24% had at least one node that was 10 cm or larger.

Of the patients who had previously received ibrutinib, four discontinued venetoclax because of progressive disease and four others had respiratory failure, multiorgan failure, death of unknown cause, or consent withdrawal. Of those who previously received idelalisib, four halted therapy because of progressive disease and failure to respond. Of 48 evaluable patients, 38 previously received ibrutinib, and 10 previously received idelalisib.

The overall response rate was 61% (23 of 38 patients) for patients refractory to ibrutinib and 50% (5 of 10 patients) for those refractory to idelalisib. A complete response was seen in three patients, all refractory to ibrutinib.

Grade 3/4 adverse events were seen in over 10% of patients and included neutropenia (39%), thrombocytopenia (22%), anemia (20%), leukopenia (13%), and pneumonia (13%). Significant adverse events seen in at least two patients included pneumonia (9%), febrile neutropenia (7%), increased potassium, multiorgan failure, and septic shock (4% each).

The study is sponsored by AbbVie.