Dan's heart is full of vitality Focus on LBCL China exploration, immune checkpoint inhibitors can be expected in the future

Since immune checkpoint inhibitors won the 2018 Nobel Prize in Physiology or Medicine, immune checkpoint inhibitors have become a core pillar

On September 7, 2022, BeiGene held the "DanXin Direction, Infinite Vitality - Immune Checkpoint Inhibitors Exploration and Exchange Meeting in the Field of Big B Cell Lymphoma" online, inviting a number of well-known experts and scholars in the field of hematology and tumors in China to talk about the progress of

The meeting kicked off

Professor Cao Yang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, made a wonderful report

*GDP±R: Gemcitabine, Dexamethasone, Cisplatin± Rituximab; BEAM: carmustine, etoposide, cytarabine, melphalan; BEAC: carmustine, etoposide, cytarabine, cyclophosphamide

Novel therapies CAR-T therapy also face many clinical challenges in R/R DLBCL, such as large masses, high tumor burden, rapid progression, and other high-risk patients who have limited

Combined with the latest progress and clinical research results, Professor Cao Yang emphasized that for the diagnosis and treatment mode of R/R DLBCL, it is first necessary to distinguish between low-risk and high-risk patients, which can be used through pathological features, lesion sites, histological features, International Prognostic Index (IPI) score, cell origin, AND FISH, second-generation gene sequencing (NGS) and other means

Brainstorming can lead to the collision of insights
.

After Professor Cao Yang shared, Professor Liu Tingbo of Union Hospital Affiliated to Fujian Medical University, Professor Li Wenyu of Guangdong Provincial People's Hospital, and Professor Sang Wei of The Affiliated Hospital of Xuzhou Medical University discussed
the clinical application of PD-1 monoclonal antibody, autologous transplantation and CAR-T therapy.

Professor Liu Tingbo discussed the application timing of PD-1 monoclonal antibody in R/R DLBCL, the application of PD-1 monoclonal antibody before CAR-T can improve the T cell function of patients, the application after CAR-T treatment can make the efficacy more durable, and overall, the addition of PD-1 monoclonal antibody can enhance the immune function of patients to achieve anti-tumor effect
.

For patients with lymphoma with central nervous system involvement in how to prevent neurotoxicity during CAR-T therapy, Professor Cao Yang said that patients with high tumor burden can take levetiracetam orally before infusion to prevent ICANS, and after infusion, patients are evaluated twice a day for CRS and ICANS neurological events, and early intervention
is required for high-risk patients.

CrS can be treated with dexamethasone or methylprednisolone, and the tumor burden of patients can be reduced by bridging radiotherapy and other means to reduce CRS
.

Subsequently, Professor Li Wenyu proposed that the efficacy of CAR-T treatment alone in central nervous system lymphoma is not ideal, and the initial efficacy of autologous transplantation combined with CAR-T treatment is better, which is worth further exploration
.

Professor Sang Wei said based on his own clinical experience that patients with good physical fitness and sensitivity to chemotherapy may be more suitable for sequential CAR-T treatment with autologous transplantation, and it is recommended to carry out CAR-T treatment for patients with poor physical fitness, large tumor burden and chemotherapy resistance, reduce tumor burden and achieve deep remission, and then sequentially autologous transplantation, which will help reduce the recurrence rate of
patients.

Professor Gao Yan of the Center for Cancer Prevention and Control of Sun Yat-sen University shared the research progress of PD-1 monoclonal antibody in DLBCL and the application experience
of the center.

The treatment status of patients with R/R DLBCL who cannot be transplanted or progressed after transplantation is not optimistic, and how to use existing drugs with high availability to bring more survival benefits to patients is an urgent problem to be solved
.

Professor Gao Yan stressed that PD-1 monoclonal antibody is an immunotherapy drug with high drug accessibility in China, and the best time and combination scheme for DLBCL treatment need to be explored, and other programs such as R-CHOP and DA-EPOCH-R are expected to make breakthroughs
in R/R DLBCL treatment.

From foreign experience, the safety of PD-1 monoclonal antibody combination therapy has been moved forward to the first-line treatment, and the overall efficacy has been initially improved
.

*R-CHOP, rituximab combined with cyclophosphamide, vincristine, doxorubicin, prednisone; DA-EPOCH-R, rituximab combined with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin

At present, the experience accumulated by the Center for Cancer Prevention and Treatment of Sun Yat-sen University in the application of PD-1 monoclonal antibody has achieved encouraging results
.

(1) The PD-1 monoclonal antibody combined with cydabenamine and rituximab (PCR) regimen had a considerable initial effect in R/R DLBCL, with an ORR of 69.
2% and a CR rate of 46.
2%.


(2) PD-1 monoclonal antibody combined with anti-CD20 monoclonal antibody sequential R-CHOP In the first-line treatment of elderly DLBCL patients with initial treatment, the ORR reached 100%, and the CR rate was as high as 87.
5%.


(3) PD-1 monoclonal antibody combined with ifosfamide, carboplatin, etoposide (ICE) in the treatment of R/R DLBCL has considerable efficacy and good safety, and the remission time of CR patients is long-lasting, of which the efficacy of non-GCB patients is more significant
.

(4) Tirelizumab combined with lenalidomide in the treatment of elderly patients with non-GCB subtype R/R DLBCL, the study shows that the patients who have been enrolled have reached CR, and the current study is still in progress, and it is expected that future evidence can further confirm the benefit
of this regimen for elderly patients.

Overall, PD-1 monoclonal antibody has a synergistic effect with a variety of drugs, and the combination of application can improve the overall efficacy, and it is believed that PD-1 monoclonal antibody will play an unprecedented important role
in the treatment of R/R DLBCL in the future.

After Professor Gao Yan's wonderful sharing, Professor Bai Qingxian of Xijing Hospital of Air Force Military Medical University, Professor Li Jie of Qilu Hospital of Shandong University, Professor Qian Zhengzi of Tianjin Cancer Hospital, and Professor Zhang Lei of the First Affiliated Hospital of Zhengzhou University launched a warm academic discussion
.

Professor Bai Qingxian proposed based on his own clinical experience that when elderly patients with T cells rich in DLBCL are treated with conventional R-CHOPE for high fever, the body temperature can return to normal after the application of tirelizumab, and PD-1 monoclonal antibody can be explored
more deeply in the T cell-rich DLBCL in the future.

In view of the significance of PD-L1 expression for the clinical application of PD-1 monoclonal antibody, Professor Li Jie pointed out that patients with high PD-L1 expression (especially >30%) have better efficacy and benefit more from PD-1 monoclonal antibody therapy, but in the clinical application of PD-1 monoclonal antibody, especially when combining drugs, it is not necessary to refer to the PD-L1 expression of patients
.

Regarding how PD-1 monoclonal antibodies are deployed in LBCL, Professor Qian Zhengzi said that the combined application of PD-1 monoclonal antibody and R-CHOP to DLBCL has achieved encouraging results, proving that the combination of PD-1 monoclonal antibody and anti-CD20 monoclonal antibody has a synergistic effect, and the glucocorticoids in it do not affect the efficacy of PD-1 monoclonal antibody
.

Professor Gao Yan added that in view of the fact that the initial efficacy of two epimodulatory drugs combined with PD-1 monoclonal antibody in the treatment of NK/T cell lymphoma (NKTCL) has been further improved, this treatment model in the future is worth looking forward to
in the field of LBCL.

For the best people to use PD-1 monoclonal antibody, Professor Zhang Lei believes that the efficacy of PD-1 monoclonal antibody may be better in patients with DLBCL of non-GCB subtype, but more studies are needed to verify
.

Finally, Professor Zou Liqun added that some subtypes of LBCL, such as LBCL in the vascular LBCL of the central nervous system, LBCL in special parts such as LBCL of the digestive tract, and LBCL with positive EBV, may be better benefited
from PD-1 monoclonal antibody.

After a warm academic collision and endless discussions, the conference came to an end
.

The president of the conference concluded that PD-1 monoclonal antibody has high accessibility, can be widely tried in the field of LBCL, and the combined regimen with rituximab, cydalbenzamine and other drugs has a considerable initial efficacy, hoping to identify the types of patients who benefit more from PD-1 monoclonal antibody in the future, and also look forward to more research data to guide the clinical application
of PD-1 monoclonal antibody.

Although the protocol of autologous transplantation combined with CAR-T treatment has a preliminary efficacy, there is still a big gap between CAR-T therapy from clinical trials to commercial promotion, and it has not yet been clear whether autologous transplantation should be carried out first or CAR-T treatment first, and further research and exploration
are still needed.

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