New Data Shows AbbVie's VENCLYXTO®/VENCLEXTA® Fixed-Duration Combination with Gazyvaro Demonstrates Durable Efficacy in First-Line CLL Treatment
Jun 15, 2021 00:23
CST Updated
00:23
AbbVie
Innovative Drug Developer
Chronic lymphocytic leukemia (CLL, image source: dxline.info)
June 14, 2021 /BioonBIOON/ -- AbbVie recently announced the 4-year follow-up analysis results of the Phase 3 CLL14 trial. The data showed that in treatment-naïve patients with comorbidities and chronic lymphocyticLeukemiaIn patients with (CLL), compared with those receiving the standard-of-care chemoimmunotherapy regimen (Gazyvaro + chlorambucil), patients receiving a fixed-duration 12-month combination regimen of Venclyxto and Gazyvaro continued to demonstrate longer progression-free survival (PFS) and a higher minimal residual disease-negative rate (MRD-negative, i.e., undetectable MRD, uMRD) three years after treatment discontinuation.
With a median follow-up of over 4 years (52.4 months), compared with the Gazyvaro + chlorambucil treatment group, the Venclyxto + Gazyvaro treatment group demonstrated a longerPFS (median: not reached vs 36.4 months)、Risk of disease progression or death reduced by 67% (HR=0.33; 95% CI: 0.25-0.45). At 4 years post-randomization, disease in the Venclyxto + Gazyvaro treatment groupThe progression-free survival rate is 74%、The Gazyvaro + chlorambucil treatment group was 35.4%. An improvement in PFS was observed across all clinical and biological risk groups, including patients with TP53 mutations, 17p deletions, and unmutated IGHV status.
In addition,At 30 months after treatment completion, peripheral blood MRD assessment showed that 26.9% of patients in the Venclyxto + Gazyvaro treatment group remained undetectable for MRD (<10^-4), compared with only 3.2% in the Gazyvaro + chlorambucil treatment group.Undetectable MRD (uMRD, also referred to as MRD-negative [MRD-]) is an objective assessment tool, defined as: using a sensitive analytical method, the proportion of residual CLL cells in blood or bone marrow is <1 per 10,000 leukocytes.
In the 4-year follow-up analysis, no new safety signals were observed. Among patients receiving Venclyxto + Gazyvaro treatment, the most frequently occurring severeAdverse Reactions(≥2%) are pneumonia, sepsis, febrile neutropenia, andTumorTumor lysis syndrome (TLS).
CLL is the most common type of leukemia in adults. It is a slow-growing leukemia characterized by the accumulation of a large number of immature lymphocytes in the blood and bone marrow. CLL accounts for approximately one-third of newly diagnosed leukemia cases. In recent years, despite advances in treatment, many patients cannot tolerate the side effects of chemotherapy-containing regimens.
Based on the results of the Phase 3 CLL14 study, the Venclyxto + Gazyvaro regimen has been approved by U.S. and European regulatory authorities for the first-line treatment of adult patients with chronic lymphocytic leukemia (CLL) with comorbidities. As a fixed-duration, chemotherapy-free regimen, Venclyxto + Gazyvaro provides an important treatment option for patients with CLL, enabling them to achieve deep remissions and sustained progression-free survival benefits, while also offering the added advantage of a finite treatment duration.
Principal Investigator of the CLL14 Study, Department of Hematology, University Hospital Cologne, GermanyTumorExpert Othman Al Sawaf stated: "CLL is considered an incurable disease, and each relapse becomes increasingly difficult to treat; therefore, the key treatment goal is to maintain remission for as long as possible. The 4-year results from the CLL14 study show that among patients receiving a fixed-duration regimen of Venclyxto plus Gazyvaro, 74% remained free of PFS events for more than 3 years after treatment cessation. This highlights the durability of remission in the vast majority of patients following 12 fixed cycles of therapy, indicating that the Venclyxto plus Gazyvaro combination is an effective option for previously untreated CLL patients."
Venetoclax is a first-in-class, oral, selective B-cell lymphoma 2 (BCL-2) inhibitor co-developed by AbbVie and Roche, with both companies jointly responsible for its commercialization in the US market (brand name: Venclexta), while AbbVie is responsible for commercialization in markets outside the US (brand name: Venclyxto). The BCL-2 protein inApoptosisplays an important role in (programmed cell death), prevents the apoptosis of certain cells (including lymphocytes), and is overexpressed in certain types of cancer, which is associated with the development of drug resistance. Venetoclax is designed to selectively inhibit the function of BCL-2, restore cellular communication systems, and enable cancer cells to self-destruct, to achieve therapeutic outcomes.Tumorpurpose.
Venetoclax has been approved in over 80 countries worldwide for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML). In the United States, venetoclax has beenFDAGranted 5 Breakthrough Therapy Designations (BTD), one for first-line treatment of CLL, 2 for relapsed or refractory CLL, and 2 for first-line treatment of acute myeloid leukemia (AML).
In China, venetoclax (Venclexta®) was approved in December 2020, in combination with azacitidine, for the treatment of patients with comorbidities that preclude intensive induction chemotherapy, or those aged 75 years or older with newlyDiagnosisadult patients with acute myeloid leukemia (AML). Venetoclax (Venclexta®, venetoclax) is China's first approved B-cell lymphoma-2 (BCL-2) inhibitor, marking the entry of China's AML field into the era of targeted therapy.
Obinutuzumab (Gazyva/Gazyvaro) is a product developed by Roche. It is the first glycoengineered type II anti-CD20 monoclonal antibody targeting the CD20 molecule on the surface of B cells, capable of directly inducing B-cell death. Obinutuzumab is designed to enhance antibody-dependent cellular cytotoxicity (ADCC) and direct cell death induction. Obinutuzumab is marketed under the brand name Gazyva in the United States and Gazyvaro in Europe. (Bioon.com)