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    Home > Active Ingredient News > Blood System > Venecla combined with ibrutinib in the treatment of relapsed and refractory chronic lymphocytic leukemia: results of phase II VISION study

    Venecla combined with ibrutinib in the treatment of relapsed and refractory chronic lymphocytic leukemia: results of phase II VISION study

    • Last Update: 2021-03-24
    • Source: Internet
    • Author: User
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    The current demand for treatment of relapsed and refractory (R/R) chronic lymphocytic leukemia (CLL) lies in the lack of a treatment plan that can provide deep relief and avoid prolonged maintenance treatment.

    At present, a number of studies are exploring the efficacy of related combination programs in R/R CLL.
    Although the combined program of venexa and rituximab can control the treatment time of R/R CLL, it cannot increase the CR rate of patients.

    The emergence of new BTK inhibitors such as ibrutinib and acalabrutinib has brought changes in the treatment of chronic lymphocytic leukemia (CLL).

    Pre-clinical studies have confirmed that venecla combined with ibrutinib has a synergistic effect in primary CLL cells and mouse models.

    Relevant studies have also confirmed the efficacy of Venecla combined with Ibrutinib in the first-line treatment of CLL.

    The Phase II VISION study explored the efficacy and safety of venecla combined with Ibrutinib in R/R CLL.
    The main results of the study are summarized as follows for the reference of readers.

    Research methods Phase II VISION study (NCT03226301) included patients who had previously received ≥1 line immunochemotherapy and were diagnosed with R/R CLL and creatinine clearance ≥30mL/min.

    The patients enrolled in the study first received 2 cycles (28-day cycle) of Ibrutinib monotherapy (420 mg/day), and in the third cycle, they received Ibrutinib treatment and at the same time received escalating doses of Venecla.
    In cycles 4-15, he received full dose (400 mg) of venecla and ibrutinib.

    After the 15th cycle of treatment was completed, patients with partial remission (PR) in blood and bone marrow tests and undetectable minimal residual disease (uMRD) were randomly assigned to receive ibrutinib maintenance treatment or watchful waiting.

    During the watchful waiting period, patients with MRD re-yang will restart the combined treatment of venexa and ibrutinib, and patients with MRD re-yang during the maintenance treatment of ibrutinib will continue to receive the maintenance treatment of ibrutinib.

    Patients with positive MRD after the 15th cycle of treatment will also receive maintenance therapy with Ibrutinib.

    Patients with disease progression during treatment will be withdrawn from the study.

    Patients who have achieved remission or received maintenance treatment after treatment with the combination regimen are not considered as disease progression if they restart treatment due to MRD re-yang.

    Study Results The study included 230 patients from July 2017 to January 2019.

    The median age of the patients included in the study was 67 years (range: 40-83 years); 71% of the patients were male; 65% of the patients had a WHO physical status score of 0; 84% of the patients had a Binet stage of B/C; 71% of patients received standard immunochemotherapy; 18% of patients had TP53 aberrations (17p deletion and/or TP53 mutation); 57% of patients had no mutation in IGHV.

    Among the 51 patients in the VISION study who underwent interim analysis, 49 patients completed the first 2 cycles of ibrutinib monotherapy, and 43 patients (84%) completed all 15 cycles of treatment.

    Among them, 27 patients (53%) achieved complete remission (CR), and 15 patients (29%) achieved PR (as shown in the figure below).

    In the first 15 cycles of treatment, the cumulative incidence of serious adverse events (SAE) was 57% (Figure A below).

    One patient died of unexplained cause during the monotherapy of Ibrutinib, and one patient died of lung cancer during the combined treatment.

    Among the adverse events of concern (≥Grade 2), 9 patients (18%) reported atrial fibrillation (1 case of grade 3, 8 cases of grade 2), and 7 patients reported bleeding (1 case of grade 3, 6 cases of grade 2) , 33 patients reported infection (1 case of grade 4, 18 cases of grade 3, 14 cases of grade 2) (Figure B below).

    The most common site of infection is the respiratory tract, followed by the urinary tract and skin (Figure C below).

    The peripheral blood remission of the patients in the study continued to improve during the treatment period: 28 patients (55%) achieved uMRD after completing 15 cycles of treatment, and 20 (39%) patients obtained bone marrow uMRD (flow cytometry 10- 4 levels, as shown below).

    The uMRD rate of this combination regimen is similar to the results of the veneclair combined with rituximab regimen in the treatment of R/R CLL published in previous related studies, and the CR rate is significantly higher.

    Among the 43 patients who completed 15 cycles of treatment, 14 patients received uMRD in both peripheral blood and bone marrow.
    These patients were randomly assigned to receive Ibrutinib maintenance treatment or watchful waiting according to a 2:1 ratio.

    The conclusions of the study The combination of venexa and ibrutinib showed a good effect in R/R CLL.
    At the same time, the safety was consistent with the results of previously reported CLL-related studies, and no new safety events were found.

     The remission rate (CR rate: 57%; PR rate: 25%) of the Venecla combined with Ibrutinib in the VISION study is similar to the results in related studies in the United Kingdom, and lower than the first-line CLL of this program The CR rate of 88% during treatment was significantly higher than the CR rate of 8.
    2% in R/R CLL with the combination of Venecla and rituximab.

    However, the uMRD rate of this combination regimen is similar to that of Veneclave combined with rituximab regimen in the treatment of R/R CLL, suggesting that different treatment regimens have different therapeutic effects for different disease sites (lymph nodes, spleen, bone marrow, and peripheral blood).

    The evaluation of MRD and curative effect should be combined with the type of targeted treatment plan, clinical curative effect and molecular characteristics of the disease.

     The follow-up of this study will explore the safe timing of withdrawal of the combination regimen of Venecla and ibrutinib.
    The study will mainly focus on: whether patients whose peripheral blood and bone marrow reach uMRD after 15 cycles of treatment do not require further treatment and wait for the MRD to re-yang during the waiting process.
    Of patients can restart treatment with venecla and ibrutinib to prevent disease progression.

    The relevant research results will be announced at the end of 2021.

    References Carsten U.
    Niemann, Mark-David Levin, Julie Dubois, Sabina Kersting, et al.
    Venetoclax and ibrutinib for patients with relapsed/refractory chronic lymphocytic leukemia.
    Blood (2021) 137 (8): 1117–1120.
    ; https: // doi.
    org/10.
    1182/blood.
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