Jain N, et al. - In this investigator-initiated phase 2 study, researchers assessed the therapeutic efficacy of combined ibrutinib (an inhibitor of Bruton’s tyrosine kinase) and venetoclax (an inhibitor of B-cell lymphoma 2 protein) in treatment-naive high-risk and older patients with chronic lymphocytic leukemia (CLL). They found combined venetoclax and ibrutinib had efficacy as an oral regimen in the treatment of high-risk and older patients with CLL.

Methods

• Presence of at least one of the following features: chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or an age of 65 years or older was required for inclusion of cases.
• Treatment regimen was: ibrutinib monotherapy (420 mg once daily) for 3 cycles, followed by the addition of venetoclax (weekly dose escalation to 400 mg once daily).
• Patients were treated with combined therapy for 24 cycles.
• Using the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria, response evaluations were carried out.
• Via multicolor flow cytometry in bone marrow (sensitivity, 10⁻⁴), minimal residual disease was evaluated.

Results

• With a median age of 65 years (range, 26 to 83), 80 patients were treated.
• The age of 30% of study sample was 70 years or older.
• Unmutated IGHV, TP53 aberration, or chromosome 11q deletion were present in 92% of the participants.
• Over time, an increase was noted in the proportions of patients who had complete remission (with or without normal blood count recovery) and remission with undetectable minimal residual disease after treatment with combined therapy.
• Researchers found that combined treatment administered for 12 cycles led to complete remission or complete remission with incomplete count recovery in 88% of the patients and remission with undetectable minimal residual disease in 61%.
• Older adults and all high-risk subgroups responded to treatment.
• Tumor lysis syndrome developed in 3 cases, as per laboratory evidence.
• The adverse-event profile displayed was similar to what has been reported with ibrutinib and venetoclax.