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    Home > Active Ingredient News > Blood System > This combination regimen may improve outcomes for patients with relapsed/refractory mantle cell lymphoma in China

    This combination regimen may improve outcomes for patients with relapsed/refractory mantle cell lymphoma in China

    • Last Update: 2023-02-03
    • Source: Internet
    • Author: User
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    Ibrutinib is an oral Bruton tyrosine kinase (BTK) inhibitor that has been widely used in the treatment
    of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).
    A phase II clinical study evaluating the efficacy and cytotoxicity of ibrutinib monotherapy as a salvage treatment for patients with MCL showed that the overall response rate (ORR) was 68%, the complete response rate (CR) was 21%, and the follow-up for 27 months showed long-lasting efficacy and good safety
    Ibrutinib was approved in China in August 2017 for the treatment of patients
    with MCL with ≥ prior treatment line number1.
    However, ibrutinib monotherapy still has limitations, including low CR rates, short progression-free survival (PFS), and the possibility
    of drug resistance.
    Several studies evaluating the efficacy of ibrutinib in combination with rituximab, lenalidomide, or venetoxle in patients with R/R MCL showed CR rates of 40% to 70%.

    At present, the actual efficacy and safety of these two regimens in Chinese patients with R/R MCL are unclear
    Based on this, 13 medical centers in China jointly participated in a national, multi-center retrospective study to explore the efficacy and safety
    of ibrutinib monotherapy and ibrutinib-based combination therapy in Chinese patients with R/R MCL.
    The main contents of Yimaitong are organized as follows

    Research methods

    This review included adult patients with R/R MCL who started ibrutinib monotherapy or ibrutinib-based combination therapy between August 2017 and December 2020
    Inclusion Criteria: (1) MCL diagnosed pathologically according to the 2016 World Health Organization classification of lymphoma; (2) Age≥ 18 years old; (3) relapse or ineffectiveness of the latest treatment plan; (4) Receiving ibrutinib monotherapy or combination therapy
    Patients were divided into ibrutinib monotherapy and ibrutinib combination according to their regimen: patients in the monotherapy group were treated with ibrutinib until disease progression, intolerable toxicity, or physician/patient choice; Patients in the combination therapy group received 4-8 courses of combination therapy with ibrutinib-based, patients who achieved at least stable disease (SD) received maintenance therapy, and those who developed disease progression during treatment received the next line of therapy
    To assess the patient's response
    to ibrutinib according to the 2014 Lugano criteria.
    Objective response rate (ORR), CR rate, time to response (TTR), duration of response (DOR), overall PFS survival (OS), reasons for discontinuation of ibrutinib, and incidence
    of adverse events (TEAEs) during treatment were assessed.

    Study results>>>>

    Clinical features

    A total of 121 patients with R/R MCL were included in this study, including 68 in the monotherapy group and 53 in
    the combination therapy group.
    The proportion of patients aged 60 years in the combination group ≥ lower than in the monotherapy group (P=0.

    There were no statistically significant differences in other baseline features between the two groups (Table 1).

    Table 1


    Treatment plan and efficacy assessment

    Forty-five patients (84.
    9%) in the combination group were treated with no chemotherapy regimen
    Ibrutinib + rituximab (IR) was the most common combination regimen (32/53, 60.
    4%), followed by ibrutinib + rituximab + lenalidomide (IR2) (10/53, 18.
    During the combination therapy, 8 patients experienced disease progression, and the remaining 45 patients achieved at least SD after 4-8 courses of treatment, and no disease progression; 91.
    1% (41/45) of patients received maintenance therapy
    The optimal ORR of 121 patients was 71.
    1%, the CR rate was 28.
    1%, and the partial response (PR) rate was 43.

    The ORR and CR rates in the combination treatment group were significantly higher than those in the monotherapy group (ORR, 84.
    9% vs 60.
    3%, P=0.
    003; CR rate, 43.
    4% vs 16.
    2%, P<0.

    The ORR and CR rates of patients in the combination treatment group who received no chemotherapy regimen were 84.
    4% and 44.

    The median TTRs were 6.
    3 months (95% CI, 4.
    1 months) and 2.
    6 months (95% CI, 2.
    5 months) in the monotherapy and combination groups, respectively (Figure 1).

    Of the 86 patients who responded to treatment, the median DOR was 14.
    8 months (95% CI, 11.
    2 to 22.
    7 months) in the monotherapy group and not in the combination group (Figure 2).

    The difference between TTR and DOR was statistically significant (TTR, P<0.
    001; DOR, P=0.

    Figure 1

    Figure 2


    Survival analysis

    With a median follow-up of 20.
    5 months (95% CI, 18.
    3 to 22.
    6 months), the estimated median PFS for all patients was 21.
    7 months (95% CI, 15.
    2 to 26.
    6 months), and the PFS rates at 1 and 2 years were 70.
    7% and 39.
    The median OS was 37.
    6 months, with 1-year and 2-year OS rates of 86.
    9% and 64.
    PFS was longer in the combination group than in the monotherapy group (30.
    8 [95% CI, 23.
    5-NE] vs 18.
    5 [12.
    1 to 21.
    8]; HR,0.
    53 [95% CI,0.
    93]; P=0.
    025) (Figure 3).

    Figure 3

    OS was not improved in the combination group compared with monotherapy (median OS did not reach [95% CI, 20.
    6-NE] vs 28.
    2 months [95% CI, 21.
    5-NE]; HR,0.
    77[95% CI,0.
    55]; P = 0.
    430) (Figure 4).

    Figure 4

    The PFS benefit of combination versus monotherapy was assessed in different subgroups based on baseline characteristics, with significant PFS benefit observed in male patients, non-refractory disease, Ki67<30%, previous treatment line = 1, ablastic subtype, and extranodal involvement site <2 (Figure 5).

    Figure 5



    At the last follow-up, 67 patients discontinued ibrutinib-based therapy, mainly due to disease progression (50/67, 74.
    Other reasons for discontinuation of ibrutinib included: treatment side effects (9/67, 13.
    4%; 2 cases of pulmonary infection, 3 cases of hemorrhage, 3 cases of secondary tumors, 1 case of ventricular premature beats and palpitations), patient or physician choice (4/67, 6.
    0%), non-MCL-related death (1/67, 1.
    5%), and unknown cause (3/67, 4.

    The incidence of neutropenia was significantly higher in the combination group than in the monotherapy group (32.
    0% vs 12.
    7%, P=0.

    Fifteen patients had abnormal ECG tests, of which 2 showed atrial fibrillation, the rest included 11 cases with atrial premature contractions, and 2 cases with premature ventricular beats
    Heavy bleeding occurred in 4 patients, 1 case of central nervous system hemorrhage, 1 case of grade 3 gastrointestinal bleeding, and 1 case
    of grade 3 subcutaneous hemorrhage.


    Mutation analysis

    In 21 available tumor samples, 446 leukemia and lymphoma-related genes were detected by NGS, and missense mutations were found to be the main type of
    gene mutation.
    The four genes with the highest mutation frequency were ATM (13/21, 61.
    9%), KMT2D (8/21, 38.
    1%), NSD2 (6/21, 28.
    6%) and SMARCA4 (5/21, 23.

    Conclusion of the study

    This multicentre retrospective study suggests that ibrutinib-based combination regimens may be superior to ibrutinib monotherapy and have an equal
    safety profile.
    Ibrutinib-based combination therapy may be one of
    the preferred treatment options for patients with R/R MCL.

    References: Yuchen Zhang, Panpan Liu, Jun Cai, et al.
    Ibrutinib as monotherapy versus combination therapy in Chinese patients with relapsed/refractory mantle cell lymphoma: A multicenter study.
    Cancer Med.
    2022 Apr 9;00:1-12.
    doi: 10.

    Approval number CN-99835, the content of this material is supported by AstraZeneca, is for the reference of medical and healthcare professionals only and is not intended for promotional purposes

    Reviewed: Wenting Typesetting: Wenting Executive: Quinta

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