Nitin Jain, MD
In a single-center phase II trial reported in The New England Journal of Medicine, Nitin Jain, MD, and colleagues found that the combination of ibrutinib and venetoclax was highly active in previously untreated high-risk and older patients with chronic lymphocytic leukemia (CLL).
In the study, 80 patients at The University of Texas MD Anderson Cancer Center, Houston, initiated treatment between July 2016 and June 2018. Patients received ibrutinib at 420 mg once daily for three 28-day cycles followed by the addition of venetoclax at a weekly dose escalation to 400 mg once daily. The combination treatment was administered for a total of 24 cycles.
The median age of patients enrolled was 65 years, with 30% aged ≥ 70 years. Overall, 92% of patients had at least one of the high-risk features of chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or age ≥ 65 years.
With combination treatment, the proportion of patients with complete remission with or without normal blood count recovery and remission with undetectable minimal residual disease increased over time. After 12 cycles, 88% of patients had complete remission or complete remission with incomplete count recovery and 61% had remission with undetectable minimal residual disease in bone marrow. After 18 cycles, the respective proportions were 96% and 69%.
Responses were observed in patients aged ≥ 65 years and in all high-risk subgroups. Estimated 1-year progression-free and overall survival rates were 98% and 99%, respectively.
Adverse events of grade ≥ 3 were observed in 60% of patients, with the most common nonhematologic events including atrial fibrillation/flutter (10%) and hypertension (10%). Grade 3 or 4 neutropenia occurred in 48% of patients, and neutropenic fever was observed in four patients. In addition, laboratory evidence of tumor-lysis syndrome was found in three patients.
The investigators concluded, “[W]e found combined ibrutinib and venetoclax to be an active regimen for high-risk and older patients with previously untreated CLL. High rates of complete response and remission with undetectable minimal residual disease in bone marrow were noted with this regimen without unanticipated toxic effects at early time points of follow-up.” ■