From the experience of the star center NKTCL, we talked about the development prospects of immune checkpoint inhibitors

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

On September 2, 2022, BeiGene held the "DanXin Direction, Infinite Vitality - Multidisciplinary Exploration and Exchange Meeting of Immune Checkpoint Inhibitors in the Field of NK/T 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

Chairman's Speech The meeting kicked off with the opening speech of Professor Li Yexiong of the Cancer Hospital of the Chinese Academy of Medical Sciences

Exploration of off-junction NKTCL diagnosis and treatment, data sharing of West China Hospital Center of Sichuan University

Professor Yang Chunli of West China Hospital of Sichuan University shared the clinical experience and related exploration

In 2011, Sichuan Huaxi Hospital took the lead in proposing the "sandwich" therapy to treat early NKTCL in the world, and the concept of "sandwich" therapy has been used by the NCCN guidelines to this day

In order to reduce the toxicity caused by radiotherapy, our department has made a preliminary exploration of NKTCL in the early stage of radiotherapy reduction treatment, and the results show that the complete response (CR) rate of patients after treatment reaches 100%.

*Modified SMILE protocol: methotrexate, calcium folinate, ifosfamide, mesna, dexamethasone, etoposide, levoastase; P-Gemox: Peppases, gemcitabine, oxaliplatin

Unlimited vitality: PD-1 antibody in the field of NKTCL Exploration Professor Zhu Zunmin of Henan Provincial People's Hospital first introduced the pathogenesis of NKTCL and the current first-line treatment plan, and based on the application experience of the center, said that the P-GemoxD protocol in early NKTCL patients is better than the CHOP-like protocol

It has been found that circulating EBV-DNA before treatment is an independent prognostic factor for NKTCL, and cyclic EBV-DNA positivity is a valuable indicator
of recurrence and poor survival.

For patients with early NKTCL whose EBV-DNA has not turned negative after 4 courses of treatment, the combination of PD-1 monoclonal antibody with the original regimen can increase the rate of negative EBV-DNA and reduce the risk of
recurrence.

Professor Zhu Zunmin elaborated on an ongoing PD-1 antibody study in the treatment of EBV-DNA-positive NKTCL patients, with a mid-term assessment of 77% CR rate, 1-year progression-free survival (PFS) rate of 83.
3%, and a 2-year OS rate of 66.
7%, with a considerable initial efficacy; Another study of PD-1 monoclonal antibody treatment of elderly patients treated with NKTCL who are intolerant to chemotherapy is also ongoing, and progress
will be shared shortly.

Each expresses his opinion

After Professor Zhu Zunmin's wonderful sharing, Professor Qi Shunan of the Cancer Hospital of the Chinese Academy of Medical Sciences and Professor Yu Wenjuan of the First Affiliated Hospital of Zhejiang University School of Medicine launched a warm academic discussion
.

Professor Qi Shunan proposed that some PET/CT positive patients did not find tumor cells when they performed lesion biopsy, which may be due to the increase in SUVmax value caused by the inflammatory response during treatment of patients, which led to false positive results of PET/CT, and recommended that NKTCL experienced doctors be consulted for secondary biopsy
.

Professor Zou Liqun added that PET/CT has poor sensitivity in NKTCL, and there are more cases of false positives in patients in the mid-term evaluation, and the clinical outcomes of positive and negative patients with PET/CT after radiotherapy are similar
.

For the clinical application of PD-1 monoclonal antibody combined with P-GemoxD protocol, Professor Yu Wenjuan shared that the application of PD-1 monoclonal antibody in patients who have reached CR but EBV is still positive can enhance the immune response effect of T cells in the body and achieve the effect of clearing EBV, such as patients who are EBV positive and have a high copy number, and early application of PD-1 monoclonal antibody
can also be considered.

Clinical research sharing from NKTCL

Professor Tao Rong of Fudan University Affiliated Cancer Hospital made a wonderful report
on the clinical research progress of NKTCL.

Professor Tao Rong first emphasized that complete PET/CT scans are crucial for the accuracy of clinical staging, and PET/CT examination needs to be more standardized and standardized, and Lugano staging is a more appropriate staging standard
.

He then introduced that the center explored the treatment mode of levoparamase-based combination chemotherapy and radiotherapy in early NKTCL patients, and the study showed that the patient had a good prognosis, reducing the intensity of cytotoxic drugs in the chemotherapy regimen did not seem to affect the patient's treatment response and survival, and the timing pattern of chemotherapy and radiotherapy needed to be further explored
.

In patients with advanced NKTCL, the center also explored the efficacy of levoparaginase-based induction chemotherapy + autologous transplant consolidation therapy, and the results showed that patients had a good prognosis and 80% of patients had a tendency to
cure.

For refractory patients, PD-1 monoclonal antibody can provide significant survival benefits that deserve further exploration
.

Professor Tao Rong believes that how to select patients who are suitable for autologous transplantation is also extremely critical, and based on the experience of the center, after 4 rounds of chemotherapy, patients who have reached CR with PET/CT assessment, bone marrow EBER and plasma EBV-DNA are negative may benefit from autologous transplantation
to the greatest extent.

In addition, the risk stratification model PINK/PINK-E can not distinguish the different prognostic risks of advanced patients very well, and the prognostic model needs to be optimized
.

Each expresses his opinion

Subsequently, Professor Fan Lei of Jiangsu Provincial People's Hospital, Professor Li Caixia of the First Affiliated Hospital of Soochow University, Professor Xu Pengpeng of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and Professor Zeng Zhiyong of the First Affiliated Hospital of Fujian Medical University held relevant discussions
.

Professor Fan Lei said that some patients with advanced NKTCL cannot undergo autologous transplantation due to the progression of disease after induction therapy, and the combination of PD-1 monoclonal antibody, asparaginase and alllotinib can improve the CR rate of patients, so that some patients who are not suitable for autologous transplantation can be converted into suitable transplantation, bringing more clinical benefits
to patients.

Subsequently, Professor Li Caixia proposed according to her own clinical experience that the maintenance treatment regimen of PD-1 monoclonal antibody was recommended for advanced patients after autologous transplantation, and the patients were well
tolerated.

Professor Xu Pengpeng said that the clinical need to continue to explore a higher safety of the treatment strategy, PD-1 monoclonal antibody and cydabenamine, asparaginase and other drugs of the combination program worth further exploration
.

For patients who have reached CR but plasma EBV-DNA is still positive, Professor Zeng Zhiyong believes that the first reason is whether the patient's tumor is not completely cleared or chronic active EBV infection, if the patient is accompanied by immunodeficiency, hemophilic syndrome and other related gene mutations, allogeneic transplantation should be performed as soon as possible, and donors with similar gene mutations need to be excluded
.

The conference concluded after a warm academic collision and unfinished discussion
.

The chair of the conference concluded that there are still many urgent problems to be solved in the field of NKTCL, including how to improve the overall cure rate in first-line treatment for advanced patients, how to reduce the long-term toxicity of treatment (such as the toxicity of radiotherapy) while ensuring the efficacy of early patients, and how to choose treatment options for asparaginase-resistant patients, which need further exploration
.

I hope that in the future, all colleagues will work together to optimize the treatment of NKTCL, and finally thank the data provided by the centers and the experience shared by the big names, and thank Baekje for providing the academic exchange platform
.

Scan the QR code to watch the highlights
of this conference Editor: Chole Reviewer: Evelyn Layout: Moly Execution: Moly

Poke "Read the original article" to see the highlights of the last meeting