Bruton’s tyrosine kinase and B-cell lymphoma-2 inhibition are thought to show complementary biological activity in treating chronic lymphocytic leukemia (CLL). At the ASH 2018 Annual Meeting, researchers reported results of an investigator-initiated phase 2 trial of combined ibrutinib (IBR) and venetoclax (VEN) as first-line treatment for patients with CLL.
To be eligible for study inclusion, all patients had at least 1 high-risk feature, which included del(17p), mutated TP53, del(11q), unmutated IGHV, or age ≥65 years. Patients received IBR monotherapy (420 mg daily) for 3 cycles followed by the addition of VEN escalated weekly to a target dose of 400 mg daily. The primary end point was complete remission (CR) or CR with incomplete bone marrow recovery (CRi).
A total of 80 patients were enrolled in the study. The median age was 65 years, with 30% of patients aged ≥70 years. Of the enrollees, 83% had unmutated IGHV, 18% had del(17p), 14% had TP53 mutation, and 25% had del(11q). The median follow-up for all patients was 14.8 months.
After 3 months of IBR monotherapy, the majority (57%) of evaluable patients showed a partial response. After the addition of VEN, increasing proportions of patients achieved CR/CRi and bone marrow undetectable minimal residual disease (BM U-MRD) remission. At 6 months of IBR-VEN treatment, 73% of patients achieved CR/CRi and 40% achieved BM U-MRD remission. At 12 months of the combination, 88% of the patients were in CR/CRi, with 61% achieving BM U-MRD remission. Older and high-risk patients showed similar response and MRD rates compared with the overall population.
During the study period, 11 (14%) patients discontinued study treatments, 5 during IBR monotherapy and 6 during the combination phase. Easy bruising, arthralgia, and diarrhea were the most common nonhematologic adverse events, each occurring in over 40% of patients. Grade 3/4 neutropenia occurred in 48% of patients. IBR was dose-reduced in 35 (44%) patients; the most common reason was atrial fibrillation, which occurred in 9 of the patients.
Researchers concluded that VEN-IBR combination therapy is an effective, safe, and chemotherapy-free oral regimen for patients with high-risk treatment-naïve CLL, with similar response in older adults and across all high-risk subgroups. Adverse event profiles were similar to what has been reported individually with IBR and VEN.
Jain N, et al. ASH 2018. Abstract 186.