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The 63rd Annual Meeting of the American Society of Hematology (ASH) was successfully held on December 11-14, 2021
.
Professor Cai Qingqing from the Cancer Center of Sun Yat-sen University and his team explored the involvement of the central nervous system in patients with extranodal nasal NK/T cell lymphoma, which was selected for this year's ASH poster presentation
.
Yimaitong invited Professor Cai Qingqing to accept an interview to talk about the treatment progress of extranodal NK/T cell lymphoma and the results and significance of this study
.
Yimaitong: Extranodal NK/T cell lymphoma is a type of aggressive lymphoma, which mainly affects the nasal cavity and nasopharynx.
Central nervous system involvement is rare
.
Could you please introduce the current status of diagnosis and treatment of patients with extranodal nasal NK/T cell lymphoma of the lower central nervous system and what are the difficulties in the diagnosis and treatment process? Professor Cai Qingqing’s incidence of malignant lymphoma is increasing year by year, and new cases rank first in hematological tumors.
Among them, extranodal nasal NK/T cell lymphoma (NKTCL) is particularly high, and it is closely related to Epstein-Barr virus infection.
It is more common in southern China, but central Nervous system violations are relatively rare
.
There are still some difficulties in the clinical diagnosis and treatment of NKTCL central invasion
.
First, there is still a lack of risk models and treatment standards for predicting NKTCL central invasion in the current clinical diagnosis and treatment process
.
Second, the diagnosis of NKTCL central nervous system invasion also has its own characteristics.
Due to the particularity of the invasion site, the diagnosis of NKTCL central nervous system invasion needs to be combined with pathological diagnosis (central lesions, cerebrospinal fluid-related pathological examination) and clinical diagnosis (diagnosis of external central lesions is On the basis of NKTCL, characteristic changes in central imaging)
.
Due to the uniqueness of clinical diagnosis and treatment of patients with NKTCL central invasion, there is an urgent need to increase the understanding of NKTCL central invasion and explore the establishment of new effective treatment models
.
Yimaitong: You and your team conducted a study to explore the clinicopathological characteristics, treatment and prognosis of patients with extranodal NK/T cell lymphoma in the central nervous system.
Could you please introduce the study first? Background and purpose? Professor Cai Qingqing’s extranodal nasal NK/T cell lymphoma (NKTCL) is an aggressive tumor that often manifests as extranodal invasion, often involving the upper respiratory and digestive tract (nasal cavity, nasopharyngeal, paranasal sinuses, palate), and the nasal cavity is the most Particularly affected areas
.
The external involvement of the nose also includes skin, soft tissue, gastrointestinal tract, and testicles
.
Compared with Europe, the incidence of extranodal NKTCL is higher in Asia and South America
.
Statistics from Gao Zifen and Sun on the distribution of lymphomas in the Chinese population found that extranodal nasal NKTCL accounts for about 6%-11% of all lymphomas, and about 28%-56% of T/NK cell lymphomas, but it involves the central nervous system.
Systematic NKTCL is relatively rare, and the incidence rate reported in previous studies is <3~7.
8%
.
In recent years, the incidence of various types of central nervous system tumors has increased, which may be related to the advancement of detection technology and the increase of people's attention
.
Due to the rarity of NKTCL central invasion and the lack of clinical data, we analyzed the clinical cases of NKTCL central invasion in our center, summarized the clinical features, diagnosis methods, treatment strategies and prognosis of this type of disease, in order to enhance the understanding of NKTCL central invasion
.
Yimaitong: What are the results of this study? What is the guiding significance for the clinic? Professor Cai Qingqing The incidence of central involvement in the 1,019 extranodal nasal NKTCL patients included in this study was 1.
3% (14 cases)
.
The median age of patients at the time of diagnosis of NKTCL central invasion was 40.
5 years
.
71.
4% (10/14) of the cases were men
.
The median time from the first diagnosis of NKTCL to the diagnosis of central invasion was 3.
0 months (0~141 months)
.
All patients underwent imaging examination, 9 patients showed central nervous system lesions on imaging examination, and 5 patients confirmed central invasion through cerebrospinal fluid cytology and flow cytometry
.
13 patients underwent cerebrospinal fluid examination, 2 patients had no abnormalities in cerebrospinal fluid, 8 patients were diagnosed with NKTCL central invasion with elevated cerebrospinal fluid protein, and 2 patients had elevated cerebrospinal fluid white blood cells
.
The median number of treatment lines after the diagnosis of NKTCL central invasion was 1.
5 (1-4)
.
The best curative effect for patients after treatment was complete remission (11 cases), 1 case had partial remission, 1 case had stable disease, and 1 case had disease progression
.
The treatment programs that patients with complete remission receive when they achieve the best effect include: high-dose methotrexate-containing regimen (5 cases), pegaspartase-containing regimen (4 cases), and anti-PD-1 monoclonal antibody-containing regimen (3 cases) , Cidaniline-containing program (2 cases)
.
The median duration of response (DOR) in patients with disease remission did not reach (1 month-NR)
.
Another 2 patients received anti-PD-1 monoclonal antibody maintenance treatment after complete remission.
Both patients did not relapse at the last follow-up of this study.
The DOR was 26 months and 72 months, respectively
.
The median DOR of patients with central invasion at first diagnosis and patients with central invasion at relapse did not reach
.
After diagnosis of NKTCL central invasion, the median follow-up time was 24.
5 months (4-72 months), 5 patients died, and the median OS did not reach (April-NR)
.
Nine patients were accompanied by increased EBV DNA load in peripheral blood when the central invasion occurred
.
After treatment, 7 patients with EBV DNA turned negative, and 6 of them achieved complete remission
.
Based on the results of this study, the diagnosis of NKTCL central invasion should be combined with clinical symptoms, imaging examinations and cerebrospinal fluid examinations for comprehensive judgment
.
The treatment effect and survival prognosis of the patients in this study have been improved compared with previous studies, suggesting that chemotherapeutic drugs such as methotrexate and pegaspase are routinely used in the treatment of NKTCL central invasion, while anti-PD-1 monoclonal antibodies and Western The application of new drugs such as dalbenamide may further improve the prognosis of patients
.
The dynamic changes of EBV DNA have a certain prompting effect on the changes of the disease state
.
Yimaitong: Could you please briefly introduce what other developments in the field of extranodal NK/T cell lymphoma are worth paying attention to in recent years? Professor Cai Qingqing aims to treat patients with early-stage NKTCL for the first time.
The current guidelines mainly recommend radiotherapy and chemotherapy.
However, the choice of treatment mode is currently unclear
.
We took the lead in establishing 7-linked single nucleotide polymorphism (SNP) prediction tags for international multi-centers, which can achieve high-precision prognostic stratification (Blood, 2021)
.
At the same time, we established the P-GemOx (peaspartase, gemcitabine, oxaliplatin) sequential radiotherapy regimen to treat patients with early NKTCL, the 5-year OS rate can reach 80%, and the toxicity is lower (Am J Hematol, 2021) Radiation field and radiation dose are the key to the success or failure of early NKTCL treatment, and are closely related to the local area control rate and prognosis of the tumor.
A study from Professor Li Yexiong’s team from the Tumor Hospital of the Chinese Academy of Medical Sciences shows that early patients are recommended to irradiate the affected field, and the recommended radical dose is 50Gy
.
For newly-treated advanced patients, we created the PD-1 monoclonal antibody combined with P-GemOx regimen to treat newly-treated advanced NKTCL patients, which can increase the overall response rate (ORR) to 88.
9%, the CR rate to 77.
8%, and tolerability Good (Signal Transduct Target Ther, 2020), and adopted by the Chinese Society of Clinical Oncology (CSCO) lymphoma diagnosis and treatment guidelines
.
For relapsed and refractory NKTCL, our research found that the ORR of PD-1 monoclonal antibody combined with histone deacetylase inhibitor chidamide was 58.
3%, and the CR rate was 44.
4%
.
The results of a national multi-center phase II clinical study showed that the ORR of mitoxantrone liposomes for the treatment of relapsed and refractory PTCL was 52.
4%, and the CR rate was 28.
6%; the ORR of relapsed and refractory NKTCL was 52.
4% (11/ 21), the CR rate is 28.
6% (6/21), the curative effect ranks first among all subtypes, indicating that chemotherapy combined with immunotherapy also has a good application prospect in relapsed and refractory NKTCL
.
With the application of second-generation sequencing technology in recent years, studies have found that genes are related to therapeutic efficacy and prognosis
.
Our previous studies have suggested that genetic changes such as PD-L1, JAK/STAT, DDX3X, TET2, KMT2D may be related to the efficacy of immunochemotherapy
.
Professor Zhao Weilai from Ruijin Hospital, Shanghai Jiaotong University School of Medicine, defined three molecular subtypes of TSIM, MB and HEA based on the biological characteristics of NKTCL, and confirmed that they are closely related to clinical prognosis and have certain reference value for future treatment options
.
Professor Qingqing Cai, Chief Physician, PhD Supervisor, Deputy Director of the Department of Internal Medicine, Sun Yat-sen University Tumor Hospital, Head of the Lymphoma Group of the Oncology Branch of the Guangdong Medical Association, Deputy Chairman of the Youth Committee of the Oncology Branch of the Chinese Medical Association, Lymphoma Major, China Medical Education Association Deputy Chairman of the Committee, Deputy Chairman of the Lymphoma Professional Committee of the Guangdong Provincial Association of Women Physicians, Deputy Chairman of the Guangdong Anti-Cancer Association Hematological Oncology Committee, Deputy Chairman of the Youth Committee, Beijing Cancer Prevention and Treatment Society, Deputy Chairman of the Lymphoma Immunization Committee of the Beijing Cancer Prevention and Treatment Association, published 79 SCI articles , Published 19 SCI papers in Blood, Leukemia, CCR, etc.
as a (co-) corresponding author in the past 5 years, presided over a number of national natural funds and provincial funds stamped "Read the original text", we make progress together
.
Professor Cai Qingqing from the Cancer Center of Sun Yat-sen University and his team explored the involvement of the central nervous system in patients with extranodal nasal NK/T cell lymphoma, which was selected for this year's ASH poster presentation
.
Yimaitong invited Professor Cai Qingqing to accept an interview to talk about the treatment progress of extranodal NK/T cell lymphoma and the results and significance of this study
.
Yimaitong: Extranodal NK/T cell lymphoma is a type of aggressive lymphoma, which mainly affects the nasal cavity and nasopharynx.
Central nervous system involvement is rare
.
Could you please introduce the current status of diagnosis and treatment of patients with extranodal nasal NK/T cell lymphoma of the lower central nervous system and what are the difficulties in the diagnosis and treatment process? Professor Cai Qingqing’s incidence of malignant lymphoma is increasing year by year, and new cases rank first in hematological tumors.
Among them, extranodal nasal NK/T cell lymphoma (NKTCL) is particularly high, and it is closely related to Epstein-Barr virus infection.
It is more common in southern China, but central Nervous system violations are relatively rare
.
There are still some difficulties in the clinical diagnosis and treatment of NKTCL central invasion
.
First, there is still a lack of risk models and treatment standards for predicting NKTCL central invasion in the current clinical diagnosis and treatment process
.
Second, the diagnosis of NKTCL central nervous system invasion also has its own characteristics.
Due to the particularity of the invasion site, the diagnosis of NKTCL central nervous system invasion needs to be combined with pathological diagnosis (central lesions, cerebrospinal fluid-related pathological examination) and clinical diagnosis (diagnosis of external central lesions is On the basis of NKTCL, characteristic changes in central imaging)
.
Due to the uniqueness of clinical diagnosis and treatment of patients with NKTCL central invasion, there is an urgent need to increase the understanding of NKTCL central invasion and explore the establishment of new effective treatment models
.
Yimaitong: You and your team conducted a study to explore the clinicopathological characteristics, treatment and prognosis of patients with extranodal NK/T cell lymphoma in the central nervous system.
Could you please introduce the study first? Background and purpose? Professor Cai Qingqing’s extranodal nasal NK/T cell lymphoma (NKTCL) is an aggressive tumor that often manifests as extranodal invasion, often involving the upper respiratory and digestive tract (nasal cavity, nasopharyngeal, paranasal sinuses, palate), and the nasal cavity is the most Particularly affected areas
.
The external involvement of the nose also includes skin, soft tissue, gastrointestinal tract, and testicles
.
Compared with Europe, the incidence of extranodal NKTCL is higher in Asia and South America
.
Statistics from Gao Zifen and Sun on the distribution of lymphomas in the Chinese population found that extranodal nasal NKTCL accounts for about 6%-11% of all lymphomas, and about 28%-56% of T/NK cell lymphomas, but it involves the central nervous system.
Systematic NKTCL is relatively rare, and the incidence rate reported in previous studies is <3~7.
8%
.
In recent years, the incidence of various types of central nervous system tumors has increased, which may be related to the advancement of detection technology and the increase of people's attention
.
Due to the rarity of NKTCL central invasion and the lack of clinical data, we analyzed the clinical cases of NKTCL central invasion in our center, summarized the clinical features, diagnosis methods, treatment strategies and prognosis of this type of disease, in order to enhance the understanding of NKTCL central invasion
.
Yimaitong: What are the results of this study? What is the guiding significance for the clinic? Professor Cai Qingqing The incidence of central involvement in the 1,019 extranodal nasal NKTCL patients included in this study was 1.
3% (14 cases)
.
The median age of patients at the time of diagnosis of NKTCL central invasion was 40.
5 years
.
71.
4% (10/14) of the cases were men
.
The median time from the first diagnosis of NKTCL to the diagnosis of central invasion was 3.
0 months (0~141 months)
.
All patients underwent imaging examination, 9 patients showed central nervous system lesions on imaging examination, and 5 patients confirmed central invasion through cerebrospinal fluid cytology and flow cytometry
.
13 patients underwent cerebrospinal fluid examination, 2 patients had no abnormalities in cerebrospinal fluid, 8 patients were diagnosed with NKTCL central invasion with elevated cerebrospinal fluid protein, and 2 patients had elevated cerebrospinal fluid white blood cells
.
The median number of treatment lines after the diagnosis of NKTCL central invasion was 1.
5 (1-4)
.
The best curative effect for patients after treatment was complete remission (11 cases), 1 case had partial remission, 1 case had stable disease, and 1 case had disease progression
.
The treatment programs that patients with complete remission receive when they achieve the best effect include: high-dose methotrexate-containing regimen (5 cases), pegaspartase-containing regimen (4 cases), and anti-PD-1 monoclonal antibody-containing regimen (3 cases) , Cidaniline-containing program (2 cases)
.
The median duration of response (DOR) in patients with disease remission did not reach (1 month-NR)
.
Another 2 patients received anti-PD-1 monoclonal antibody maintenance treatment after complete remission.
Both patients did not relapse at the last follow-up of this study.
The DOR was 26 months and 72 months, respectively
.
The median DOR of patients with central invasion at first diagnosis and patients with central invasion at relapse did not reach
.
After diagnosis of NKTCL central invasion, the median follow-up time was 24.
5 months (4-72 months), 5 patients died, and the median OS did not reach (April-NR)
.
Nine patients were accompanied by increased EBV DNA load in peripheral blood when the central invasion occurred
.
After treatment, 7 patients with EBV DNA turned negative, and 6 of them achieved complete remission
.
Based on the results of this study, the diagnosis of NKTCL central invasion should be combined with clinical symptoms, imaging examinations and cerebrospinal fluid examinations for comprehensive judgment
.
The treatment effect and survival prognosis of the patients in this study have been improved compared with previous studies, suggesting that chemotherapeutic drugs such as methotrexate and pegaspase are routinely used in the treatment of NKTCL central invasion, while anti-PD-1 monoclonal antibodies and Western The application of new drugs such as dalbenamide may further improve the prognosis of patients
.
The dynamic changes of EBV DNA have a certain prompting effect on the changes of the disease state
.
Yimaitong: Could you please briefly introduce what other developments in the field of extranodal NK/T cell lymphoma are worth paying attention to in recent years? Professor Cai Qingqing aims to treat patients with early-stage NKTCL for the first time.
The current guidelines mainly recommend radiotherapy and chemotherapy.
However, the choice of treatment mode is currently unclear
.
We took the lead in establishing 7-linked single nucleotide polymorphism (SNP) prediction tags for international multi-centers, which can achieve high-precision prognostic stratification (Blood, 2021)
.
At the same time, we established the P-GemOx (peaspartase, gemcitabine, oxaliplatin) sequential radiotherapy regimen to treat patients with early NKTCL, the 5-year OS rate can reach 80%, and the toxicity is lower (Am J Hematol, 2021) Radiation field and radiation dose are the key to the success or failure of early NKTCL treatment, and are closely related to the local area control rate and prognosis of the tumor.
A study from Professor Li Yexiong’s team from the Tumor Hospital of the Chinese Academy of Medical Sciences shows that early patients are recommended to irradiate the affected field, and the recommended radical dose is 50Gy
.
For newly-treated advanced patients, we created the PD-1 monoclonal antibody combined with P-GemOx regimen to treat newly-treated advanced NKTCL patients, which can increase the overall response rate (ORR) to 88.
9%, the CR rate to 77.
8%, and tolerability Good (Signal Transduct Target Ther, 2020), and adopted by the Chinese Society of Clinical Oncology (CSCO) lymphoma diagnosis and treatment guidelines
.
For relapsed and refractory NKTCL, our research found that the ORR of PD-1 monoclonal antibody combined with histone deacetylase inhibitor chidamide was 58.
3%, and the CR rate was 44.
4%
.
The results of a national multi-center phase II clinical study showed that the ORR of mitoxantrone liposomes for the treatment of relapsed and refractory PTCL was 52.
4%, and the CR rate was 28.
6%; the ORR of relapsed and refractory NKTCL was 52.
4% (11/ 21), the CR rate is 28.
6% (6/21), the curative effect ranks first among all subtypes, indicating that chemotherapy combined with immunotherapy also has a good application prospect in relapsed and refractory NKTCL
.
With the application of second-generation sequencing technology in recent years, studies have found that genes are related to therapeutic efficacy and prognosis
.
Our previous studies have suggested that genetic changes such as PD-L1, JAK/STAT, DDX3X, TET2, KMT2D may be related to the efficacy of immunochemotherapy
.
Professor Zhao Weilai from Ruijin Hospital, Shanghai Jiaotong University School of Medicine, defined three molecular subtypes of TSIM, MB and HEA based on the biological characteristics of NKTCL, and confirmed that they are closely related to clinical prognosis and have certain reference value for future treatment options
.
Professor Qingqing Cai, Chief Physician, PhD Supervisor, Deputy Director of the Department of Internal Medicine, Sun Yat-sen University Tumor Hospital, Head of the Lymphoma Group of the Oncology Branch of the Guangdong Medical Association, Deputy Chairman of the Youth Committee of the Oncology Branch of the Chinese Medical Association, Lymphoma Major, China Medical Education Association Deputy Chairman of the Committee, Deputy Chairman of the Lymphoma Professional Committee of the Guangdong Provincial Association of Women Physicians, Deputy Chairman of the Guangdong Anti-Cancer Association Hematological Oncology Committee, Deputy Chairman of the Youth Committee, Beijing Cancer Prevention and Treatment Society, Deputy Chairman of the Lymphoma Immunization Committee of the Beijing Cancer Prevention and Treatment Association, published 79 SCI articles , Published 19 SCI papers in Blood, Leukemia, CCR, etc.
as a (co-) corresponding author in the past 5 years, presided over a number of national natural funds and provincial funds stamped "Read the original text", we make progress together
