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