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.
Patients can be successfully managed with minimal opioid medication after urologic oncology surgery, said Kerri Stevenson, MN, NP-C, RNFA, CWOCN, Lead Advanced Practice Provider – Interventional Radiology, Stanford Health Care, CA, at the 2018 ASCO Quality Care Symposium. She presented results from a 4-month study conducted at Stanford Health Care. Over the course of the study, patients were able to decrease their opioid use after surgery by 46%, without compromising pain control.
Mechanism of Pathway: Considerations of Cytogenetic and Molecular Mutation Status for Patients with Acute Myeloid Leukemia: A Deeper Look at the Role of Diagnostic and Ongoing Testing Across the Care Continuum
Acute myeloid leukemia (AML) is a heterogeneous disease that is characterized by uncontrolled proliferation of undifferentiated myeloid progenitors. While these leukemic blasts accumulate in the bone marrow and peripheral blood, impairment of normal hematopoiesis may lead to a reduction in the number of differentiated myeloid cells (granulocytes, neutrophils, monocytes, erythrocytes, megakaryocytes). Associated symptoms and consequences include anemia, bleeding, and an increased risk for infection.