Atlanta, GA—Venetoclax (Venclexta) plus rituximab (Rituxan) achieved superior progression-free survival (PFS) and overall survival (OS) compared with standard-of-care bendamustine (Treanda/Bendeka) plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). PFS improved by 81% and OS by 52% with venetoclax plus rituximab, and the depth of response was impressive—complete response and complete response with incomplete platelet recovery was 26.8%, and minimal residual disease negativity in peripheral blood was 83.5%.
These findings from an interim analysis of the phase 3 clinical trial MURANO were reported at ASH 2017.
“This is the first randomized trial comparing any of the new agents targeted to treat CLL against a standard chemoimmunotherapy program, and it has proved the superiority of the chemotherapy-free approach,” said lead investigator John F. Seymour, MBBS, PhD, FRACP, Director, Haematology Department, Peter MacCallum Cancer Centre, Melbourne, Australia.
“These findings suggest that venetoclax plus rituximab could be a standard option for relapsed or refractory CLL. There is also evidence of eradication of detectable disease that opens the prospect of time-limited therapy in this setting,” Dr Seymour continued.
A total of 389 patients were randomized to oral venetoclax 400 mg once daily, given until disease progression or unacceptable toxicity, for a maximum of 2 years, plus rituximab for 6 cycles versus 6 cycles of bendamustine plus rituximab. In the venetoclax arm, the dose was gradually increased to 400 mg daily over 4 to 5 weeks to reduce the likelihood of tumor lysis syndrome.
All patients had 1 to 3 previous lines of therapy. Approximately 27% of patients in both arms had deletion 17p.
The median PFS was not yet reached in the venetoclax arm versus 17 months in the bendamustine arm at a median follow-up of 23.8 months, representing an 83% risk reduction for disease progression favoring the experimental arm (P <.0001). The PFS results were consistent across subgroups, with responses seen in patients with poor-risk cytogenetics, as well as in those with good or intermediate risk.
The secondary end points favored the venetoclax arm, including OS. Patients who received venetoclax plus rituximab had a 52% reduced mortality risk. At 2 years of follow-up, the median OS was not reached in either arm.
Serious adverse events were reported in 46% of patients receiving venetoclax plus rituximab versus in 43% of those receiving bendamustine plus rituximab. Grades 3 and 4 adverse events were reported in 82% and 70% of patients, respectively. The causes of death were balanced between the 2 arms.
Grades 3 and 4 neutropenia were more common in the venetoclax arm than in the bendamustine arm (58% vs 39%, respectively). Infections were relatively infrequent. Tumor lysis syndrome occurred in 3% of patients in the venetoclax arm versus in 1% of patients in the bendamustine arm.
“Today’s phase 3 MURANO study suggests that venetoclax/rituximab will be practice-changing. We are getting away from chemotherapy and avoiding alkylating agents,” said ASH Secretary Robert A. Brodsky, MD, who moderated the press briefing.