As reported in The Lancet Oncology by Kater et al, the phase IIIb VENICE-1 trial has shown activity of venetoclax monotherapy in adult patients with relapsed or refractory

chronic lymphocytic leukemia, including those with prior B-cell receptor–associated kinase (BCR) inhibitor treatment.

Study Details

In the international multicenter trial, 258 patients were enrolled between June 2016 and March 2022, including 191 without and 67 with prior BCR inhibitor treatment. Presence of del(17p) or TP53 aberrations was permitted.

Patients received a 5-week ramp-up to 400 mg of venetoclax once daily and were treated for up to 108 weeks. The primary outcome measure was rate of complete remission or complete remission with incomplete marrow recovery in BCR inhibitor–naive patients.

Responses

Median follow-up in the total population was 49.5 months (interquartile range [IQR] = 47.2–54.1 months), including 49.2 months (IQR = 47.2–53.2 months) in the BCR inhibitor–naive group and 49.7 months (IQR = 47.4–54.3 months) in the BCR inhibitor–experienced group.

Among 191 BCR inhibitor–naive patients, 66 (35%, 95% confidence interval [CI] = 27.8%–41.8%) had complete remission or complete remission with incomplete marrow recovery, including complete remission in 31%. Among 67 BCR inhibitor-experienced patients, 18 (27%, 95% CI = 16.8%–39.1%) had complete remission or complete remission with incomplete marrow recovery, including complete remission in 25%. An additional 51% of patients in the BCR inhibitor–naive group had partial remission, yielding an overall response rate of 85%. An additional 37% of patients in the BCR inhibitor–experienced group had partial remission, yielding an overall response rate of 64%.

Median progression-free survival was 28.8 months (95% CI = 22.2–31.8 months) in the BCR inhibitor–naive group and 23.4 months (95% CI = 16.8–33.8 months) in the BCR inhibitor–experienced group. Median overall survival was not estimable (95% CI = not estimable to not estimable) and not estimable (95% CI = 37.4 months to not estimable).

Adverse Events

Grade ≥ 3 adverse events were reported in 79% of the total population, most commonly neutropenia (37%), anemia (13%), and thrombocytopenia (13%). Serious adverse events were reported in 53%, most commonly pneumonia (8%) and febrile neutropenia (6%). Adverse events led to death in 13 patients (5%), with 1 (due to autoimmune hemolytic anemia) considered possibly related to venetoclax. No new safety signals were identified.

The investigators concluded: “These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCR [inhibitor]-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCR [inhibitor]-naive and BCR [inhibitor]-pretreated patients.”

Francesco Forconi, MD, of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AbbVie. For full disclosures of the study authors, visit thelancet.com.