medwireNews: Treatment with venetoclax plus rituximab results in significantly higher rates of progression-free survival (PFS) than standard chemoimmunotherapy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), phase III MURANO trial results indicate.
Patients who received the BCL2 inhibitor venetoclax plus rituximab had a 2-year investigator-assessed PFS rate of 84.9% compared with 36.3% for those receiving the standard chemoimmunotherapeutic regimen of bendamustine plus rituximab. A similar benefit was seen across all prespecified subgroups, including patients with and without chromosome 17p deletion, according to results published in The New England Journal of Medicine.
Prespecified secondary endpoints, including the overall response rate and overall survival, “also showed consistent patterns of clinically meaningful benefit with venetoclax plus rituximab,” the study authors remark.
This international trial recruited 389 adults with relapsed or refractory CLL who had received up to three previous treatments. Participants were randomly assigned to receive either daily oral venetoclax for up to 2 years or intravenous bendamustine on days 1 and 2 of each 28-day cycle for six cycles, with both groups also receiving rituximab for the first 6 months. Venetoclax was started at 20 mg/day in a 5-week “ramp-up” period and gradually increased to a maximum of 400 mg/day, and patients underwent prophylaxis and monitoring for tumor lysis syndrome.
No new safety signals were observed with either regimen, and tumor lysis syndrome of grade 3 or 4 occurred in six patients (3.1%) in the venetoclax group and two (1.1%) in the bendamustine group. “The relatively small number of patients in the venetoclax–rituximab group who had the tumor lysis syndrome shows the effectiveness of the risk-mitigation procedures that were implemented during the trial and the generally safe delivery of the treatment in a multinational trial,” say the researchers.
At 9 months, 62.4% of patients in the venetoclax group showed clearance of minimal residual disease, compared with 13.3% of patients in the bendamustine group, and the higher rate of clearance in the venetoclax group was maintained over time.
Commenting on this, lead author John Seymour (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) and colleagues note: “The high rates of clearance of minimal residual disease that were observed in the venetoclax–rituximab group exceed those previously attained with other agents and combinations of agents in trials of relapsed or refractory [CLL] or small lymphocytic lymphoma, findings that suggest that greater efficacy results can be attained by replacing chemotherapy with venetoclax than by adding other targeted agents to chemoimmunotherapy.”
They add that the high rate “may indicate improved disease control over a longer term even when therapy is discontinued. Additional follow-up will be needed to assess the durability of such responses.”
By Catherine Booth
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