echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Antitumor Therapy > [EHA Hotspot] Median follow-up of 4 years: Otuzumab-Veneclax fixation course can continue to benefit CLL patients

    [EHA Hotspot] Median follow-up of 4 years: Otuzumab-Veneclax fixation course can continue to benefit CLL patients

    • Last Update: 2021-06-30
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com

    CLL14 is a prospective, multi-center, open-label, randomized phase III clinical study designed to evaluate a fixed course of Venexa-Otuzumab (Ven-Obi) vs.
    Chlorambucil-Otuzumab The efficacy and safety of the (Clb-Obi) regimen in patients with chronic lymphocytic leukemia (CLL) who have not been treated in the past and have comorbidities (Figure 1)
    .

    The results of the previous 2 years of follow-up showed that the Ven-Obi regimen significantly improved the progression-free survival (PFS) (88% vs 64%), and the proportion of patients with undetectable minimal residual disease (uMRD) after a fixed course of Ven-Obi treatment for 1 year Higher, can help CLL patients achieve deep relief
    .

    At present, all patients have stopped the study and treatment for at least 3 years.
    The editor will show you the updated 4-year follow-up results of the CLL14 study at this year's EHA and ICML conferences
    .

    Figure 1: The CLL14 study design was followed up for a median of 4 years.
    The 432 patients enrolled in the Ven-Obi regimen with PFS continued to be better were randomly assigned to receive the Ven-Obi regimen or the Clb-Obi regimen at a ratio of 1:1
    .

    After a median follow-up of 52.
    4 months, compared with Clb-Obi, Ven-Obi's PFS continued to be better (not reaching the median (NR) vs.
    36.
    4 months; hazard ratio [HR]: 0.
    33; 95% CI: 0.
    25-0.
    45; p<0.
    0001) (Figure 2)
    .

    Four years after randomization, the estimated PFS rates of the Ven-Obi group and Clb-Obi group were 74.
    0% and 35.
    4%, respectively
    .

    This improvement was observed in all clinical and biological risk groups, including TP53 mutation/deletion (4-year PFS rate: 53.
    0% vs 20.
    8%) and IGHV unmutated (4-year PFS rate: 68.
    0% vs 19.
    8%) The patient (Figure 3/4)
    .

    Figure 2: PFS in the Ven-Obi group continued to outperform the Clb-Obi group Figure 3: Ven-Obi regimen still outperforms the Clb-Obi regimen in patients with TP53 mutation/deletion Figure 4: Ven-Obi regimen in patients without IGHV mutation The efficacy is still better than that of the Clb-Obi regimen.
    The Ven-Obi regimen has a longer MRD doubling time and can induce sustained remission (EoT) 30 months after the end of treatment (EoT).
    26.
    9% of patients still have uMRD (<10-4), 21.
    8% of patients have low (L)-MRD (≥10-4 and <10-2), and 13.
    4% of patients have high (H)-MRD (≥10-2), while the Clb-Obi group was 3.
    2% (7 cases) uMRD, 8.
    8% L-MRD and 28.
    2% H-MRD (Figure 5)
    .

    Figure 5: The proportion of patients reaching uMRD at the end of Ven-Obi induction therapy is higher.
    Subsequently, the researchers conducted exploratory analysis and established biological models of MRD growth kinetics in CLL14 patients after stopping treatment.
    Ven-Obi group 153 cases and Clb- 154 patients in the Obi group were included in this analysis
    .

    The median MRD level at EoT after Ven-Obi treatment was significantly lower than that of Clb-Obi (10-6.
    00 vs 10-3.
    26, p<2e-16)
    .

    And at the end of treatment in the Ven-Obi group, there was no difference in MRD values ​​between patients with low-risk and high-risk characteristics, such as IGHV status (mutated IGHV is 10-5.
    79; unmutated IGHV is 10-6.
    12) or TP53 is missing/ Mutations (10-5.
    38 for deletions/mutations, 10-6.
    03 for non-deletions/mutations)
    .

     The median MRD doubling time after Ven-Obi regimen treatment was significantly longer than Clb-Obi regimen treatment (median 84 days vs 67 days, p=3.
    3e-5); Ven-Obi treatment increased from EoT to MRD level to 10 The median time of -2 was also significantly longer than Clb-Obi treatment (median 1225 days and 227 days, p<2e-16) (Figure 6) Figure 6: The median MRD doubling time was longer after induction therapy in the Ven-Obi group Based on the covariate screening of 28 biological and clinical characteristics, the final MRD growth kinetic model showed that Ven-Obi treatment, high MRD level at the beginning of treatment, high CLL-IPI, 11q loss, higher tumor burden, treatment response and IGHV status has a significant impact on MRD growth kinetics (Figure 7)
    .

    Patients with TP53 deletion/mutation also had higher MRD growth, but due to the small number of patients, it did not reach statistical significance
    .

    Figure 7: MRD growth kinetics model shows that many factors affect MRD.
    There is no significant difference in overall survival between Ven-Obi and Clb-Obi groups.
    No difference in overall survival rate between Ven-Obi and Clb-Obi groups is observed; At a median follow-up of 4 years, 85.
    4% of patients in the Ven-Obi group survived, and 83.
    1% of the patients in the Clb-Obi group survived (HR: 0.
    85[0.
    54-1.
    35]; p=0.
    49) (Figure 8)
    .

    Forty patients (18.
    9%) and 30 patients (14.
    0%) in the Ven-Obi group and Clb-Obi group reported second primary malignancies
    .

    No new safety signals were observed
    .

    Figure 8: There is no significant difference in overall survival between Ven-Obi and Clb-Obi groups.
    Summary CLL14 study 4 years follow-up confirmed that compared with Clb-Obi, fixed course of Ven-Obi treatment has longer PFS and higher MRD negative rate , So that patients can get more lasting and deeper relief
    .

    Most patients did not relapse 3 years after completing Ven-Obi treatment
    .

    Based on the analysis of the research population, a stable MRD growth kinetic model was established, describing the growth trajectory of the MRD after the treatment was stopped, and showing that compared with genotoxic chemoimmunotherapy, BCL2 targeted therapy can more effectively regulate MRD growth
    .

    In summary, a fixed course of Ven-Obi is an effective treatment for patients with comorbid CLL
    .

    References: 1.
    EHA-S146 Venetoclax-Obinutuzumab for previously untreated chronic lymphocytic leukemia: 4-year follow-up analysis of the randomized CLL14 study.
    2.
    EHA-EP632 Venetoclax-Obinutuzumab modulates clonal growth: results of a population-based minimal residual disease model from the randomized CLL14 study.
    Stamp "read the original text" and we will make progress together
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.