Venetoclax plus Rituximab New Chemotherapy-Free Option for Chronic Lymphocytic LeukemiaLeukemia, Web Exclusives
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.
According to the FDA’s “Center for Drug Evaluation and Research (CDER) Annual Report: New Drug Therapy Approvals 2019,” the agency approved 48 novel drugs in 2019. Although this number does not approach the record of 59 approvals in 2018, it far surpasses the mere 22 approvals that occurred in 2016.
New Clues to Mismatch Repair and PD-1/PD-L1 Status and Survival in Patients with Gastric or Esophageal Cancer
San Francisco, CA—Understanding the complex relationship between the PD-1 receptor, its ligand 1 (PD-L1), and mismatch repair deficiency (dMMR) status may help to improve treatment outcomes in patients with resectable gastric and esophageal cancer, according to a retrospective tissue-based analysis.