Cramer P, et al. - Given that, in chronic lymphocytic leukemia, obinutuzumab (type II anti-CD20 antibody) and venetoclax (B-cell lymphoma-2 antagonist) have shown remarkable therapeutic activity, researchers assessed the combined efficacy of these two agents in patients with chronic lymphocytic leukemia. They reported no unexpected or cumulative toxicities resulted from the sequential application of bendamustine and obinutuzumab combined with venetoclax. They also noted that regardless of physical fitness and genetic risk factors, a high proportion of both treatment-naive and relapsed or refractory patients who achieved overall responses compared favorably to established chronic lymphocytic leukemia therapies.

Methods

• This is an ongoing multicenter, open-label, investigator-initiated phase 2 trial.
• In this trial, enrollment of patients (aged ≥ 18 years) with chronic lymphocytic leukemia requiring treatment according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance status of 0–2 was carried out at 16 sites in Germany.
• They administered sequential treatment of debulking with two cycles of bendamustine (70 mg/m²intravenously on days 1 and 2 of each of the two 28-day cycles), followed by induction and maintenance with obinutuzumab (1000 mg intravenously on days 1–2, 8, and 15 of the first induction cycle, every 4 weeks in induction cycles 2–6, and every 12 weeks in the maintenance phase) and oral venetoclax (starting in induction cycle 2 with 20 mg/day, with a weekly dose escalation over 5 weeks to the target dose of 400 mg/day) to patients with a relevant tumor load (absolute lymphocyte count ≥ 25,000 cells per μL or lymph nodes with a diameter of ≥ 5 cm).
• The proportion of patients achieving an overall response by investigator assessment at the end of induction treatment was the primary endpoint.
• Efficacy analyses involving all patients who received at least two induction cycles and safety analyses including all patients who received at least one dose of study drug were performed.

Results

• A total of 66 patients were enrolled (35 treatment naive and 31 with relapsed or refractory disease) between May 6, 2015 and January 4, 2016.
• Of these subjects, three were excluded from the efficacy analysis because they received fewer than two induction cycles.
• According to data, 34 (54%) of the remaining 63 patients in the efficacy-evaluable population were treatment naive and 29 (46%) had relapsed or refractory disease.
• Induction treatment was completed by all patients at data cutoff (February 28, 2017).