Venetoclax chemotherapy-free combination regimen for patients with previously untreated chronic lymphocytic leukemia
Data from the CLL14 trial, the first randomized clinical trial to examine stopping an oral-based, chemotherapy-free combination after 12 months in previously untreated patients with chronic lymphocytic leukemia ( CLL ) and coexisting medical conditions were presented at the American Society of Clinical Oncology ( ASCO ) Annual Meeting and were simultaneously published in the New England Journal of Medicine ( NEJM ).
The results have demonstrated that Venetoclax ( Venclyxto ) plus Obinutuzumab ( Gazyvaro ) prolonged progression-free survival ( PFS ) and achieved higher rates of complete response and minimal residual disease ( MRD )-negativity compared to a commonly used standard of care Obinutuzumab plus Chlorambucil.
The Venetoclax and Obinutuzumab combination was recently approved by the U.S. Food and Drug Administration ( FDA ) for previously untreated patients with CLL or small lymphocytic lymphoma ( SLL ) based on results from the CLL14 clinical trial.
In the CLL14 trial, investigator-assessed results have demonstrated that patients with CLL who were treated with Venetoclax plus Obinutuzumab have achieved superior progression-free survival compared to patients treated with Obinutuzumab plus Chlorambucil.
Twenty-four-month PFS estimates were 88.2% and 64.1%, respectively ( hazard ratio [ HR ]: 0.35, 95% confidence interval [ CI ]: 0.23, 0.53; P less than 0.001 ).
Higher rates of MRD-negativity were observed with Venetoclax plus Obinutuzumab compared to Obinutuzumab plus Chlorambucil in both peripheral blood ( 75.5% versus 35.2%, P less than 0.001 ) and bone marrow ( 56.9% versus 17.1% [ P less than 0.001 ] ) three months after treatment completion, and complete response rates were significantly higher with Venetoclax plus Obinutuzumab than with Chlorambucil plus Obinutuzumab ( 49.5% versus 23.1% [ P less than 0.001 ] ).
In the CLL14 trial, the adverse events were consistent with the known safety profiles of Venetoclax and Obinutuzumab alone.
At least one adverse effect of any grade occurred in 94.3% of patients in the Venetoclax plus Obinutuzumab arm.
The most common grade 3/4 adverse effects in patients receiving Venetoclax plus Obinutuzumab were febrile neutropenia ( 5.2% ) and infections ( 17.5% ).
Tumor lysis syndrome ( TLS ) was reported in three patients in the Venetoclax plus Obinutuzumab group ( all during treatment with Obinutuzumab and before Venetoclax ).
None of these events met the Howard criteria for clinical TLS.
The prospective, multicenter, open-label, randomized phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group ( DCLLSG ), has evaluated the efficacy and safety of a combined investigational regimen of Venetoclax plus Obinutuzumab ( n=216 ) versus Obinutuzumab plus Chlorambucil ( n=216 ) in previously untreated patients with CLL and coexisting medical conditions.
The therapies were administered for a finite duration of 12 months for Venetoclax in combination with six cycles of Obinutuzumab.
The trial enrolled 432 patients, all of whom were previously untreated according to the International Workshop on Chronic Lymphocytic Leukemia ( iwCLL ) criteria.
The primary endpoint was progression-free survival based on investigator assessment, using iwCLL criteria.
Key secondary endpoints were PFS as assessed by an independent review committee, MRD-negativity in peripheral blood and bone marrow, overall and complete response rates ( OR and CR rates, respectively ), MRD-negativity in complete response in peripheral blood and bone marrow, and overall survival ( OS ).
Venetoclax is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 ( BCL-2 ) protein.
In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis.
Venetoclax targets the BCL-2 protein and works to help restore the process of apoptosis. ( Xagena )
Source: Abbvie, 2019
Venetoclax ( Venclexta ) in newly-diagnosed AML patients who are ineligible for intensive chemotherapy is supported by data from a...
UCSD ( University of California San Diego ) researchers have identified the molecular mechanism activated by the presence of tetrahydrocannabinol...
European Commission has approved Venclyxto plus Gazyvaro for adults with previously untreated chronic lymphocytic leukaemia
The European Commission has approved Venclyxto ( Venetoclax ) in combination with Gazyvaro ( Obinutuzumab ) for the treatment of...
monarchE trial: Abemaciclib given with endocrine therapy has shown improvement compared to endocrine therapy alone in people whose HR+ HER2- early breast cancer is at a high risk of recurrence
Abemaciclib ( Verzenio ) in combination with standard adjuvant endocrine therapy has met the primary endpoint of invasive disease-free...
Venclexta as a chemotherapy-free combination regimen for previously untreated chronic lymphocytic leukemia patients, approved by FDA
The U.S. Food and Drug Administration ( FDA ) has approved Venclexta ( Venetoclax ) in combination with Obinutuzumab (...
The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation, proliferation, metabolism and apoptosis. Increasing body of data...
Acute myeloid leukemia ( AML ) remains a highly resistant disease to conventional chemotherapy, with a median survival of only...
Combination therapy based on Tafinlar and Mekinist for adjuvant treatment of BRAF V600 mutation-positive melanoma: approved in European Union
The European Commission has approved Tafinlar ( Dabrafenib ) in combination with Mekinist ( Trametinib ) for the adjuvant treatment...
In 2016, the National Institute for Health and Care Excellence ( NICE ) approved the use of Belimumab ( Benlysta...