2022 CSCO Professor Hu Yi: Optimized management, accurate future, full management of immunotherapy and the road to the future

The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
in Beijing on November 5.
The conference focuses on the clinical frontier of oncology, invites well-known experts and scholars at home and abroad to make wonderful progress reports or lectures, and strives to comprehensively and accurately reflect new concepts and new trends
in the field of clinical oncology.
During the meeting, Yimaitong was honored to invite Professor Hu Yi from PLA General Hospital to share how to better manage the whole process of immunotherapy in clinical practice, and looked forward to the future trend
of precision immunotherapy.

Expert profiles

Professor Hu Yi

• Director of the Department of Oncology of PLA General Hospital

• Chief physician and doctoral supervisor

• Director of the Key Laboratory of Oncology of the Ministry of Education and the All-Army Key Laboratory of Oncology

• Head of the Oncology Professional Group of the Clinical Trial Pharmacology Base of PLA General Hospital

• Director of the Department of Respiratory Oncology and Endoscopic Intervention

• Consultation experts of the Central Health Commission, advanced individuals of central health care

• Consultation expert of the Health Commission of the Central Military Commission

• Associate Editor of PLA Medical Journal

• Chairman of the Geriatric Cancer Prevention and Treatment Professional Committee of the Chinese Society of Clinical Oncology (CSCO).
  

• Chairman of the Molecular Oncology and Immunotherapy Professional Committee of the Chinese Research Hospital Association

• Vice Chairman of Oncology Branch of Beijing Medical Association

• Director of the Chinese Society of Clinical Oncology (CSCO).
  

• Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Committee

• Member of the Standing Committee of the Small Cell Lung Cancer Committee of the Chinese Society of Clinical Oncology (CSCO).
  

• Member of the Standing Committee of the Sarcoma and Melanoma Special Committee of the Chinese Society of Clinical Oncology (CSCO).
  

• Standing Committee Member of the Respiratory Endoscopy Association of the World Endoscopy Association

• Member of the Standing Committee of the Multidisciplinary Diagnosis and Treatment Committee of Oncology of the Chinese Medical Doctor Association

• Member of Oncology Branch of Chinese Medical Association

• Review expert of the National Natural Science Foundation of China

• Executive Editor of JCO Chinese Lung Cancer Special Issue

Recently, the study released by the International Conference showed that immunotherapy can increase the 5-year OS rate of advanced NSCLC to more than 20%, and advanced lung cancer is becoming a "chronic disease", please talk about from the perspective of whole-process management, from diagnosis to treatment decision-making, what measures or ways can make patients more benefits, and make advanced lung cancer truly become a "chronic disease"?

Professor Hu Yi

PLA General Hospital

From the traditional only three major methods of chemotherapy, surgery and radiotherapy, to the current targeted therapy and immunotherapy, with the continuous enrichment of treatment methods, the treatment of lung cancer has made great progress
.
The era of chemotherapy alone in patients with no driver mutations is a thing of the past, and immunotherapy has enabled these patients to survive
longer.
This benefit is for people who are candidates for immunotherapy
.
At present, it seems that immune monotherapy is also being replaced by immune combinations, and from the perspective of benefits, combination therapy covers a wider range of people, treatment response, and overall survival, which are encouraging progress
.

In the field of lung cancer, which is the most active in immunotherapy, patients can survive longer through more abundant treatment methods, so that the transformation from "talking about cancer discoloration" to "chronic disease" becomes a reality
.

First of all, in terms of diagnosis, the clinical practice has changed from previous imaging and pathological diagnosis to the current molecular typing diagnosis and immunodiagnosis
.
After the precision diagnosis platform is applied to the clinic, the diagnosis before the implementation of treatment is more accurate, which has surpassed the traditional clinical pathological diagnosis
.
In addition, molecular typing can guide not only targeted therapy, but also immunotherapy, and the efficiency of combination therapy and monotherapy can be improved
.

Second, treatment is carried out in a preferred population: first, the maximum benefit of treatment can be achieved; Second, for immunotherapy, clinicians need to try to avoid treatment-induced adverse events, although the incidence is not high, but immune-related inflammation may be more uncontrollable
.
From diagnosis to treatment to avoiding risk factors that may cause adverse events, lung cancer treatment will be more precise
.

Recently, our team has also carried out a study on negative indicators of immunotherapy, which is currently progressing smoothly, and I hope that the results can be published as soon as possible, and there is hope that immunotherapy
can be more accurately guided in the future.

Professor Hu Yi pointed out that in the case of whole-process management, clinicians are concerned about maximizing
the benefits of treatment.
We all want to bring deeper responses and longer survival
to our patients.
After tumors really become "chronic diseases", in fact, it is more necessary to pay attention to the control of
adverse events.
Clinicians need to consider the issue of "hyperprogression" in immunotherapy, which requires fine observation and biomarker guidance in clinical practice, as well as early intervention
.

Professor Hu Yi pointed out that the great progress in the field of precision treatment, better control of adverse events, early warning of serious adverse events, monitoring of immune progress and other factors are conducive to turning lung cancer into a "chronic disease"
.
Precise measures in the long-term management process will allow patients to achieve both a long survival and a very good quality of life
.

Yimaitong: You have deep knowledge in basic research, translational research, clinical research and other fields, and biomarkers guide the selection of immunologically beneficial populations and post-drug resistance decision-making is one of
the current problems.
Specific to clinical practice, what are the usual manifestations of first-line immunotherapy-resistant patients, and how should follow-up decision-making and treatment be made to achieve "optimal" management?

Professor Hu Yi

PLA General Hospital

The current immunotherapy strategy, immune checkpoint inhibitors, is actually a non-specific treatment, and immunotherapy has not yet reached a very precise era
.
The exploration of immune drug resistance is a large research topic, and the revelation of the mechanism of drug resistance will: first, it is conducive to improving the level of immunotherapy; Second, it is conducive to more accurate implementation of immunotherapy
.

Compared with chemotherapy and targeted therapy, immunotherapy causes similar results, both manifested as tumor progression, aggravation of symptoms, and poor quality of life, but immunotherapy has some particularities, such as super-progression - may cause patients to deteriorate rapidly in the short term, and even life-threatening
.
Our team is also currently conducting research related to "hyperprogression", we hope to explain the mechanism of hyperprogression by detecting a number of immune indicators, changes in the immune microenvironment, single-cell sequencing, chromatographic detection and other technologies, and avoid the occurrence
of hyperprogression as much as possible.

Immunotherapy may also produce "pseudoprogression", which is easier to manage, and most patients with pseudoprogression appear to progress radiographically only for a period of time, but are quickly replaced
by longer, deeper remissions.
In such patients, although an enlarged lesion is observed on radiography, the patient's quality of life is maintained very well and the symptoms are reduced
.
In addition to the most appropriate method of tissue biopsy, PET-CT will also help clinicians to judge, and blood ctDNA detection is also conducive to identifying disease conditions, predicting drug resistance, and identifying false progression
.

Professor Hu Yi pointed out that drug resistance is a fatal problem in tumor treatment, and if the problem of drug resistance is solved, clinical treatment strategies will produce revolutionary changes
.
For the judgment of drug resistance and the exploration of drug resistance mechanism, a lot of research
is required.
At present, international and domestic research centers are investing more efforts, and the depth of research is becoming more and more eye-catching
.

Yimaitong: Could you please talk about the current problems or challenges in immunotherapy for lung cancer, and the future research direction?

Professor Hu Yi

PLA General Hospital

Targeted therapy is mainly based on the mining
of driver genes.
Find the driver gene, and the researchers will develop the corresponding drug
accordingly.
The advantages of targeted drugs lie in three points: simplicity, precision, and good
efficacy.
However, in clinical practice, there are fewer patients with driver gene mutations, and immunotherapy has played a compensatory role on the other hand, promoting the progress of
treatment.
In the field of immunotherapy, the current means are still relatively few, and the "weapons" in our hands are limited, and now there are only PD-1/PD-L1 monoclonal antibodies or other immune checkpoint inhibitors
.
Although international and domestic immune drugs continue to emerge, these are all overlapping drugs of the same "platform
".

For now, we hope that immunotherapy will be more precise
in the future.
First, biomarkers are needed to guide existing treatments; Second, immunotherapy methods need to be abundant, bispecific antibodies, multi-target antibodies are also constantly coming out, which can enrich the current therapeutic "arsenal", but has not fundamentally changed the status quo
.

At present, the main contribution of CAR-T therapy is in the field of hematological tumors, in the future, if cell therapy can make breakthroughs in solid tumors, it will be a radical strategy for tumor treatment, and we hope that the application of CAR-T cell therapy can expand from hematological tumors to complex solid tumors
.
Researchers are working tirelessly, and the search for "epitope antigens" is becoming more and more accurate
.

T cell therapy has a "ceiling" limit, T cell killing tumors can not expand indefinitely, and unlimited expansion will affect normal
tissues.
Professor Hu Yi pointed out that NK cells kill tumor cells more accurately, the killing efficiency of CAR-NK will be greatly improved, and the impact of NK on normal tissues is very small
.
In the future, in the era of immunotherapy after immune checkpoint inhibitors, cell therapy will improve the accuracy of immunotherapy and realize the transition
from individualized immunotherapy to mechanized production immunotherapy.
Immunotherapy will likely reach the "precision" level of molecular-like targeted therapy, and we look forward to the era of precision immunity coming as soon as possible
.