Combination obinutuzumab, ibrutinib, and venetoclax induced durable remissions in patients with treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), according to results presented at the 2022 ASCO Annual Meeting.
The study included adults with treatment-naïve and relapsed/refractory CLL or small lymphocytic leukemia. Patients received venetoclax 400 mg orally daily, ibrutinib 420 mg orally daily, and obinutuzumab 1,000 mg intravenously during 28-day cycles.
Primary results of the phase Ib trial were previously reported. This phase II extended follow-up (data as of January 3, 2022) comprised 25 relapsed/refractory patients who were followed for a median of 55.8 months (range, 0.2-64.6 months), 25 treatment-naïve patients (TN1) who were followed for a median of 57 months (range, 7.4-63.2 months), and a new cohort of 25 treatment-naïve patients (TN2) who were followed for a median of 29.7 months (range, 23.6-35.0 months).
Among all 75 patients, median age was 58 years (range, 24-77 years), and 75% (n=55) had unmutated immunoglobulin heavy chain gene.
Overall response rate was 88% in the relapsed/refractory cohort, 84% in the TN1 group, and 96% in the TN2 cohort. Partial responses were observed in 44%, 52%, and 60% of patients, respectively.
Minimal residual disease was undetectable in 28% of relapsed/refractory patients, 28% of TN1 patients, and 20% of TN2 patients. At the end of treatment, 50% of patients in the relapsed/refractory cohort, 67% in TN1, and 65% in TN2 had no detectable CLL in the blood or bone marrow.
Median progression-free survival (PFS) and overall survival (OS) were not reached. Estimated 48-month PFS was 96% in both the relapsed/refractory and TN1 cohorts. Estimated 48-month OS was 85% in the relapsed/refractory cohort and 100% in the TN1 cohort. Estimated 24-month PFS and OS in the TN2 group were both 96%.
Three deaths occurred (one in each treatment cohort), and six patients experienced disease progression (four in the relapsed/refractory cohort and one in TN1). The most common adverse events were neutropenia (95%), leukopenia (95%), lymphopenia (93%), and thrombocytopenia (91%). Grade ≥3 hypertension occurred in 85% of patients, and atrial fibrillation occurred in 11%.
This triplet combination is now being studied in two phase III first-line trials.
The study was funded by Genentech.
Rogers KA, Huang Y, Abruzzo L, et al. Four-year follow-up from a phase 2 study of obinutuzumab, ibrutinib, and venetoclax in CLL. Abstract #7540. Presented at the 2022 American Society of Clinical Oncology Annual Meeting, June 3-7, 2022.