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    Home > Active Ingredient News > Blood System > Qunyinghui No. 12 Literature Intensive Reading of a New Exploration of the Treatment of Invasive Lymphoma

    Qunyinghui No. 12 Literature Intensive Reading of a New Exploration of the Treatment of Invasive Lymphoma

    • Last Update: 2022-10-03
    • Source: Internet
    • Author: User
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    "Qunying Hui - Lymphoma Diagnosis and Treatment Research Interpretation Series" is an exclusive academic exchange platform for young and middle-aged hematology doctors, through intensive reading of influential research literature in the field of lymphoma, discussing hot topics in lymphoma diagnosis and treatment, and jointly exploring and summarizing the optimal diagnosis and treatment strategies of lymphoma to improve the survival rate



    Professor Huang Wenrong of the General Hospital of the Chinese People's Liberation Army and Professor Peng Zhigang of the First Affiliated Hospital of Guangxi Medical University served as the chairmen of the conference, Professor Li Jing of the First Affiliated Hospital of Guangxi Medical University and Professor Huang Chen of the Fourth Hospital of Hebei Medical University interpreted the cutting-edge literature in the field of invasive lymphoma for everyone, and invited Professor Yi Shuhua of the Hematology Hospital of the Chinese Academy of Medical Sciences, Professor Wang Xinhua of the First Affiliated Hospital of Zhengzhou University, Professor Sun Ying of Chifeng City Hospital and Professor Zhao Donglu of the Harbin Institute of Hematology and Oncology to participate in the exchange and discussion.



    Literature Intensive Reading (1)

    DLBCL treatment of new drugs, clinical treatment how to line up the army?


    Professor Li Jing shared an article published by the Journal of Hematology & Oncology entitled "New agents and regimens for diffuse large B cell lymphoma"[1



    DLBCL treatment needs new exploration


    In recent years, to improve prognosis in patients with non-germinal center B cell sample (non-GCB) or activated B cell sample (ABC) subtype DLBCL, some randomized clinical studies have added new targeted drugs (R-CHOP+X mode) to the R-CHOP model, such as bortezomib, lenalidomide, or ibratinib


    * R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; DA-EPOCH-R: Dose-adjusted new drugs for etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab have emerged, leading to new treatment options



    In recent years, Polatuzumab Vedotin (Pola), Selinisol, tafasitamab, and targeted CD19 CAR-T have been approved by the FDA for DLBCL therapy, and a variety of targeted immune checkpoints, tumor microenvironments, molecular signaling pathways, epigenetic mutations, and cellular immunotherapy treatments have combined to form a new pattern


    Figure 1 New drugs and strategies



    ADC: In 2019, the FDA approved CD79b-targeting ADC drugs Pola in combination with phendamustine and rituximab (Pola-BR) for use in patients with


    * R-CHP: rituximab, cyclophosphamide, doxorubicin, prednisone; G-CHP: optizumab, cyclophosphamide, doxorubicin, prednisone


    CAR-T therapy: Axi-cel, liso-cel, and tisa-cel have been shown to be effective
    in targeted CD19 CAR-T cell therapy.

    In the ZUMA-1 study, patients with refractory invasive B-cell non-Hodgkin lymphoma (NHL) who had previously received at least three treatment regimens had an ORR of 83% with a CR rate of 54% and a significant improvement
    in overall survival (OS).

    Other studies have shown that CAR-T cells combined with PD-1/PD-L1 inhibitors for the treatment of R/R DLBCL appear to be feasible
    .

    The exploration of the dual target CAR-T and general-purpose CAR-T targeting CD19 and CD20/CD22 in B-cell lymphoma is promising and can become a second-line or even first-line treatment for
    high-risk patients in the near future.

    BiTE: Bellintosumab is a CD19/CD3 BiTE approved by the FDA for the treatment of R/R-B cell acute lymphoblastic leukemia
    .

    A phase II study showed that Bellintoxumab monotherapy for R/R invasive B-cell lymphoma is effective and can bridge autologous hematopoietic stem cell transplantation (ASCT).

    Immunomodulatory drugs: lenalidomide as an immunomodulator, monotherapy or combined salvage chemotherapy (e.
    g.
    , R-ICE and R-ESHAP) has been shown to be effective
    against R/R DLBL.

    The efficacy of the chemotherapy-free regimen R2 (rituximab + lenalidomide) in elderly patients with R/R DLBCL was also demonstrated, with 35% achieving persistent CR, making R2 a treatment option
    for older patients who did not qualify for ASCT.

    In addition, lenalidomide has the ability to penetrate the blood-brain barrier and has been shown to have high activity
    against primary central nervous system lymphoma (PCNSL).

    Therefore, the addition of lenalidomide to immunochemotherapy may reduce the risk of CNS recurrence, which will be validated
    in the future.

    * R-ICE: rituximab, ifosfamide, etoposide, carboplatin; R-ESHAP: rituximab, etoposide, dexamethasone, cytarabine, cisplatin

    Although some new molecular typing systems have emerged in recent years, about half of patients cannot be classified into specific subtypes, and the application of these molecular subtypes in routine clinical practice needs more research to explore
    .

    There is still a long way to go to cure DLBCL, and it is believed that the best combination of new and traditional drugs will emerge under the guidance of detailed genetic information to promote precise treatment
    of DLBCL patients.

    Expert hot discussions

    After Professor Li Jing's wonderful interpretation, many experts discussed
    the application prospects of various new drugs in DLBCL.

    Professor Peng Zhigang believes that in DLBCL treatment, it is first necessary to evaluate the prognosis and stratification of patients to guide individualized treatment
    .

    Professor Wang Xinhua proposed that the current clinical application of CAR-T is mainly limited by its higher selling price, and it is believed that with the promotion of market competition and the development of more clinical research, the accessibility of CAR-T will gradually increase
    .

    Professor Yi Shuhua believes that the current research data shows that CAR-T and new immunotherapy drugs such as Pola, bispecific antibody Glofitamab and Mosunetuzumab have performed well, and will occupy a dominant position
    in the deployment of DLBCL treatment plans in the future.

    For patients who are resistant to CAR-T, the efficacy
    can be improved in the future by designing better targets or combining them with new drugs such as Pola.

    Literature Intensive Reading (2)

    The BR regimen first-line treatment of transplant-appropriate MCL is comparable to other common chemotherapy regimens

    Professor Huang shared an article published by Blood Advances entitled "Bendamustine or high‐dose cytarabine‐based induction with rituximab in transplant‐eligible mantle cell lymphoma (BR or R-DHAP protocol induces retrospective analysis of transplant-appropriate mantle cell lymphoma [MCL])" [2] article
    .

    This study confirms that the BR regimen sequential ASCT plus rituximab maintenance therapy (MR) is a viable and effective first-line treatment with results comparable
    to the R-CHOP or R-DHAP regimen in combination with ASCT.

    * BR: rituximab, phendamustine; R-DHAP: Research background on rituximab, cisplatin, cytarabine, dexamethasone

    The standard first-line regimen for young patients with MCL is rituximab plus cytotoxic chemotherapy sequential ASCT followed by MR
    .

    Studies have shown that in patients eligible for transplantation, the BR regimen is similar to R-CHOP in terms of remission rate, ASCT success rate, or treatment outcome, and is less
    toxic.

    However, BR has never been compared
    with R-CHOP or R-DHAP as induction therapy prior to ASCT.

    This study explored the differences
    in treatment outcomes between BR and R-CHOP and r-DHAP regimens in first-line treatment in patients eligible for transplantation.

    Research Methods

    The study retrospectively analyzed
    97 patients with stage II-IV MCL aged 18-65 years who received BR treatment sequentially through ASCT and MR and 232 MCL patients in the R-CHOP/R-DHAP+ASCT group of the European MCL Younger study.

    Ann Arbor stages, lactate dehydrogenase, MCL International Prognosis Index (MIPI), blastotypic/polymorphic cell morphology, and MCL35 scores were similar
    baselines in both groups.

    However, the BR group had a higher proportion of adverse prognostic features, including poor physical status and elevated
    Ki67.

    The primary endpoint was the risk ratio (HR) of PFS between the two groups, and the secondary endpoint included the response rate
    .

    Table 1 Baseline characteristics of patients

    Results of the study

    There was no statistically significant difference
    between the BR group and the R-CHOP/R-DAP group in PFS before correction (HR 0.
    87 [95% CI 0.
    53 to 1.
    41], P=0.
    56) or after correction (HR 0.
    79 [95% CI 0.
    45 to 1.
    37], P=0.
    40).

    Figure 2 Two sets of PFS results

    Secondary endpoints were comparable in efficacy in both groups (ORR, 90% vs 94%; CR rate, 54% vs 54%), the incidence of stem cell undermobilization in the BR group was lower in patients who achieved CR or partial remission (PR) after treatment (0 vs 8.
    5%)
    .

    The proportion of patients who successfully performed ASCT after induction therapy in the two groups was 77% and 78%, respectively; The proportion of patients with BR receiving MR was significantly higher (78% vs 2%, P<0.
    001), as shown in Table 2
    .

    Table 2 Remission rate, sequential treatment after induction therapy, and outcomes

    Studies have shown that the BR regimen is safe to use in outpatients with less
    toxicity than the R-CHOP/R-DHAP group, although there are no detailed toxicity data in the BR group.

    Conclusion of the study

    BR-sequential ASCT plus MR may be a reasonable first-line treatment option for younger patients with MCL who are eligible for transplantation
    .

    Compared to the R-CHOP/R-DHAP protocol, the BR protocol is safe to use in the outpatient clinic and is less
    toxic.

    The combination of BR and new drugs will become the future trend
    of MCL treatment.

    Expert hot discussions

    After Professor Huang Chen's wonderful interpretation, a number of experts discussed
    the BR scheme and the exploration of ASCT.

    Professor Sun Ying believes that the BR regimen is a good treatment option for elderly patients who cannot tolerate large doses of cytarabine and patients who are not suitable for transplantation, and in young MCL patients suitable for transplantation, immunochemotherapy regimens containing phendamustine may be considered to move forward to first-line therapy
    .

    Professor Huang Wenrong said that some traditional beliefs that BR schemes affect stem cell collection lack relevant evidence-based medical evidence
    .

    Professor Zhao Donglu proposed that many patients in the clinic have a low acceptance of ASCT, based on the results of the window-2 study, even if the low-risk patients of MCL do not receive chemotherapy, they can have a longer PFS after treatment with rituximab combined with ibratinib and vernecla, which suggests that future attenuated chemotherapy or no chemotherapy regimens may also prolong patient survival
    .

    In addition, it is also worth looking forward to moving the treatment line of new drugs such as Pola forward, while paying attention to the long-term adverse effects
    of new drugs.

    Professor Huang Chen added that long-term application of the BR regimen may cause leukocyte reduction, which in turn will cause weakening of humoral immune function and increase the risk of infection of patients, so patients need to be closely monitored
    .

    Past Review Group Elite No.
    1 | Literature Intensive Reading at the beginning of the treatment of DLBCL diagnosis and treatment of new thinking
    group Yinghui · No.
    2 | Literature Intensive Reading Focuses on the Treatment
    of Indolent Lymphoma Group Yinghui No.
    3 | Literature Intensive Reading of Rituximab Refractory INHL Treatment of New Advances
    in the Treatment of Elite Avia No.
    4 | Literature Intensive Reading of Relapse Refractory DLBCL Treatment New Progress
    Group Yinghui No.
    5 | Literature Intensive Reading Focuses on the Treatment of CLL

    Issue 6 | Literature intensive reading of the application of anti-CD20 in lymphoma

    Issue 7 | Literature intensive reading of phendamustine combined with anti-CD20 monoclonal antibody protocol in iNHL

    Issue 8 | Optizumab plus chemotherapy first-line treatment of FL and MCL in the literature

    Issue 9 | Literature Intensive Reading on the Advanced Path to First-Line Therapy for DLBCL

    Issue 10 | A new direction for targeted treatment of B-cell lymphoma in the literature

    Issue 11 | Literature intensive reading of the treatment options for NHL patients after rituximab resistance

    Reference[1] Liang Wang, Lin-rong Li, Ken H.
    Young.
    New agents and regimens for diffuse large B cell lymphoma.
    J Hematol Oncol 13, 175 (2020).
    [2] Villa D, et al.
    Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma.
    Blood Adv.
    2022 Apr 19:bloodadvances.
    2022007371.
    Editor: Chole, Su Meng Reviewer: Evelyn Typesetting: Wenting Execution: moly

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