Prof. Zhu Jun: Innovative therapies keep up with the international frontiers, and take stock of the updated 2022 CSCO guidelines for diffuse large B-cell lymphoma

The frontier introduction is based on evidence-based medical evidence, coordinating the availability of diagnosis and treatment products, and absorbing the latest medical progress.
The annual update of the Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines has been widely praised and paid attention by the clinic
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The recent epidemic is fierce, but with the joint efforts of experts, the 2022 edition of the CSCO Lymphoma Diagnosis and Treatment Guidelines has arrived as scheduled
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Diffuse large B-cell lymphoma (DLBCL) is the most common pathological subtype of non-Hodgkin's lymphoma (NHL).
R-CHOP regimen (rituximab + cyclophosphamide + doxorubicin + vincristine) Alkali + prednisone) is the current standard regimen for the treatment of DLBCL; recently, the results of a large phase III clinical study of the CD79b-targeting antibody-drug conjugate (ADC) Polatuzumab Vedotin ("Pola") were published.
CHOP cornerstone status challenges
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Coinciding with the release of the 2022 version of the CSCO Lymphoma Diagnosis and Treatment Guideline, Yimaitong sincerely invites Professor Zhu Jun from Peking University Cancer Hospital to interpret the updated highlights in the field of DLBCL in this guideline, and combine clinical practice to share the importance of these innovative therapies for the treatment of DLBCL.
meaning
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On April 23-24, 2022, the China Society of Clinical Oncology (CSCO) Guidelines Conference, which has attracted much attention from the industry, was grandly held in Beijing in a combination of online and offline
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In the special session of hematology and tumor of this conference, Prof.
Ma Jun from Harbin Institute of Hematology and Oncology and Prof.
Zhu Jun from Peking University Cancer Hospital gave opening speeches respectively, emphasizing the importance of the guidelines in the standardization of clinical diagnosis and treatment, and hoped that the CSCO guidelines can be helpful for hematologists.
Provide guidance on diagnosis and treatment, prolong the survival of patients with blood diseases, and contribute to the realization of the ambitious goals of 2030
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Immediately afterwards, well-known scholars from all over the country briefly shared the updates of several guidelines such as lymphoma and the newly added guidelines for CAR-T cell treatment of hematological malignancies
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Among them, the updated content of DLBCL in the "2022 CSCO Lymphoma Guidelines" has attracted the attention of many experts and scholars in the industry.
Therefore, Yimaitong has organized this part of the content for readers! Update points for lymphoma pathology The 2022 version of the CSCO guidelines has been updated in lymphoma pathology, adding the "CD79b" marker
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The CD79b protein is a B-cell surface antigen that is part of the B-cell receptor (BCR); it is expressed at all stages of mature B-cells except plasma cells and is found in approximately 96% of B-cell malignancies, After binding to the antibody, it is rapidly endocytosed and delivered into the lysosome 1-4
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Based on this, CD79b becomes a potential target for targeted delivery of cytotoxic agents, which is of particular importance in drug development in the field of non-Hodgkin's lymphomas such as DLBCL
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In the chapter on the treatment of newly diagnosed DLBCL, Professor Song Yuqin once again emphasized the importance of stratified treatment based on age and prognosis for newly diagnosed DLBCL patients
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In addition, the Pola combination therapy regimen was written into the CSCO guideline for the first time; this CSCO guideline recommended the treatment of newly diagnosed DLBCL earlier than the NCCN guideline.
guide
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The new guideline recommends that 6Pola-R-CHP+2R combination therapy can be performed for newly diagnosed DLBCL patients aged ≤60 years, regardless of whether their aaIPI score is intermediate-low risk, intermediate-high risk or high-risk (category 1A, level II recommendation); For newly-treated DLBCL patients aged 60-80 years without cardiac insufficiency, 6Pola-R-CHP+2R combination therapy can also be performed (class 1A, level II recommendation)
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It is reported that the addition of Pola to the initial treatment recommendation for DLBCL patients is mainly based on a global, multi-center, phase III clinical study, the POLARIX study.
Reported in the Late-breaking Abstract (LBA) section
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During the meeting, Prof.
Song Yuqin also pointed out that the Pola-R-CHP combination therapy is expected to become a new first-line treatment option for DLBCL patients.
Therefore, it is warmed up in this guideline
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Update on the treatment of relapsed and refractory DLBCL In the chapter on the treatment of relapsed and refractory DLBCL (R/R DLBCL), many newly approved or currently unapproved drugs have been added, such as ADCs targeting CD79b, CAR-T cells, nuclear export Inhibitors, mAbs/ADCs targeting CD19,
etc.

 For R/R DLBCL patients, the new version of the guideline adds treatment recommendations based on CAR-T cells, Pola combined with bendamustine and rituximab (Pola-BR)
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CAR-T cell therapy is recommended for transplant-eligible DLBCL patients with initial relapse/progression (class 1A, level II recommendation); CAR-T cell therapy is also recommended for transplant-eligible DLBCL patients with ≥2 relapses/progressions Cell therapy (category 2A, level II recommendation)
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For DLBCL patients with initial recurrence/progression or ≥2 recurrences/progressions who are not eligible for transplantation, the Pola-BR regimen is recommended for treatment (class 2A, level II recommendation).
BR regimen, CAR-T cells or Other targeted drugs for treatment (category 2A, level II recommendation)
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Some of the preliminary related studies of these drugs added in this guideline have been completed, and some of them are expected to end this year.
At present, some patients can be treated with drugs through special channels such as free trade zones.
Therefore, the treatment for R/R DLBCL patients The above recommendations are made to provide more treatment options for this group of patients
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Expert Comments on Professor Zhu Jun Although R-CHOP is the current standard regimen for the treatment of DLBCL, 30% to 40% of patients still suffer from drug resistance and recurrence.
In the past 20 years, experts and scholars have also conducted research on the R-CHOP regimen.
Many R-CHOP+X explorations have failed to demonstrate significant clinical benefits
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 Pola is an ADC drug that targets CD79b and directly delivers the MMAE (monomethylauristatin E) carried into tumor cells.
It is also the world's first approved ADC drug in the field of DLBCL.
Based on the early key research of GO29365 , Pola has been approved for marketing in the United States in June 2019, in combination with bendamustine and rituximab (Pola-BR) for relapsed or refractory patients who have received at least two previous treatments Diffuse large B-cell lymphoma, not specified (DLBCL, NOS) in adults
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 The global phase III POLARIX study on Pola combination therapy announced at the 2021 ASH meeting is the first study to improve the efficacy of the R-CHOP regimen among all large-scale clinical research results worldwide in recent years, which not only breaks through the classics in the field of DLBCL treatment The "ceiling" of first-line treatment has also brought a new dawn to newly diagnosed DLBCL patients
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Based on this, in this year's CSCO guideline update, we are also one step ahead of the international NCCN guideline and classify the Pola-R-CHP combination therapy plan into the "official consensus"
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At present, CDE has accepted the listing application of Pola in 1L DLBCL and R/R DLBCL, so that it is expected to land in China as soon as possible to benefit more Chinese patients; it also looks forward to the approval of more new and good drugs in the future.
The survival of lymphoma patients is extended! Expert Profile Professor Zhu Jun, Secretary of the Party Committee of Peking University Cancer Hospital, Director of the Department of Internal Medicine, Director of the Lymphoma Department, and Executive Director of the Council of the Chinese Society of Clinical Oncology (CSCO) Vice Chairman of the Beijing Heathco Clinical Oncology Research Foundation Chairman of the China Anti-Lymphoma Alliance Vice President of Beijing Anti-Cancer Association President of Beijing Cancer Rehabilitation Association President of Chinese Medical Association Oncology Branch Standing Committee Member of National Health Commission Capacity Building and Continuing Education Oncology Expert Committee Member of Hematology Oncology Group Leader Reference: 1.
Shiori Hashimoto, etc.
Alternative splicing of CD79a (Ig-a/mb-1) and CD79b (Ig+/B29) RNA transcription in human B cells.
Molecular Immmology, 1995, 32, 651-659.
2.
DornanD, etc.
Therapeutic potential of an anti-CD79b antibody- drug, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma.
Blood, 2009, 114(13): 2721-9.
3.
PfeiferM, etc.
Anti-CD22 and anti-CD79B antibody drug conjugates are active indifferent conjugates Molecular diffuse large B-cell lymphoma subtypes.
Leukemia, 2015, 29(7): 1578-86.
4.
Tilly H, et al.