2022CSH| Professor Sun Chunyan: Application and research progress of circulating tumor plasma cell detection in the clinical diagnosis and treatment of multiple myeloma

Multiple myeloma (MM) is a class of clonal plasma cell abnormal proliferation of malignant blood diseases, the incidence is located in the second place of hematologic system tumors, its clinical manifestations vary greatly, the prognosis has significant heterogeneity, so MM's disease diagnosis, prognostic judgment and efficacy evaluation are particularly important
.
In recent years, with the introduction of the concept of non-invasive examination, researchers have conducted extensive research on peripheral circulating tumor plasma cells (CPCs) in MM patients, which has promoted the application
of CPCs detection in MM.

Recently, the much-anticipated "17th National Hematology Academic Conference of the Chinese Medical Association" was grandly held, and many domestic and foreign experts jointly discussed the cutting-edge progress
of blood diseases.
On this occasion, Professor Sun Chunyan of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology was invited to be interviewed to share the application and research progress
of CPC cs detection in the clinical diagnosis and treatment of MM.

With the introduction of the concept of non-invasive examination, liquid biopsy technology has become more and more
used in clinical practice.
MM, as the second largest tumor in the hematology, CPCs have received increasing attention
from clinical experts in recent years.
Can you talk about the relationship between CPCs and MM and what are their applications in MM treatment?

During tumor development, a single cell spreads from the primary tumor into the circulating cells, called circulating tumor cells
.
Circulating tumor cells colonize in different places in the body and may be the main way the tumor metastasizes far away
.
In the process of MM occurrence and development, with the progression of the disease, malignant plasma cells can enter the peripheral blood from the bone marrow to form a circulating malignant plasma cell, that is, CPCs, which is also an important way for
MM to appear distant metastasis and extramedullary infiltration.

According to the analysis of clinical studies, CPCs play an important role
in the screening and prognostic judgment of plasma cell diseases.
Previous studies have shown that CPCs can be detected in all stages of monoclonal gamma globulin disease (MGUS), smoke-emitting myeloma (SMM), and active MM, and the number of CPCs is important correlated with plasma cell disease progression, so CPCs detection can be applied to the screening
of plasma cell tumors.

Second, for SMMs, previous studies have shown that the presence of CPCs may be a high-risk prognostic factor for SMMs to progress to active MM
.
Therefore, CPCs can assess the prognosis of patients with SMM, and the monitoring of CPCs may also be one of the indicators of
SMM follow-up.

In addition, for the number of CPCs at the initial diagnosis of active MM and the change in the number of CPCs after treatment, many studies at home and abroad have confirmed that CPCs are independent prognostic factors for
patients.
Therefore, for patients with active MM, in addition to prognostic judgment, CPCs may also be able to replace bone puncture for efficacy evaluation at some treatment nodes, but how to develop the detection node at present needs more clinical research to further answer
.

You published a study last year using flow cytometry to detect CPCs in peripheral blood, could you please share your experience in carrying out CPCs and the precautions in the process of CPCs testing?

At present, the CPCs test in our department is mainly evaluated at the time of diagnosis of active MM patients to analyze the relationship between the number of CPCs and the prognosis of patients, and to establish a prognostic model
for MM patients.
Because CPCs testing is noninvasive, CPCs are also performed each time a patient undergoes hematuria assessment in subsequent efficacy evaluations in order to better explore the correlation between changes in the
number of CPCs and efficacy.

Last year, our center published a study on the relationship between peripheral blood CPCs and MM patients, mainly to clarify the prognostic value of pre-treatment CPCs levels for newly diagnosed MM patients, and to build and validate nomogram prediction models containing CPCs to individually predict the survival
of newly diagnosed MM patients.
In this study, 191 patients with MM who were treated in our hospital were included, and were divided into training cohorts and validation cohorts, and the number of
peripheral blood CPCs in patients was detected using flow cytometry.
The cut-off value of CPCs was defined as 0.
038% in the study, and the study found that CPCs were a poor prognostic factor
for MM independence.
At the same time, according to the CPCs, lactate dehydrogenase and creatinine levels and other indicators, a line chart
for predicting PFS and OS was established.
Next, our hospital is also preparing to work with other hospitals in the United Nations to establish standards for the detection of CPCs in peripheral blood and further explore the application
of CPCs in MM patients.

There are three main precautions for carrying out the detection of CPCs: (1) Establish a reasonable detection time point in the clinical design; (2) In addition, the selection of the tablet protocol for flow cytometry testing needs to be combined with the antibodies currently available in flow cytometry laboratories, and also combined with international MM standards; (3) The positive rate of CPCs testing in active MM should be increased as much as possible and form a standard testing process
in the laboratory.

Medical Pulse Pass: CPC S testing has been carried out in some centers in China, what problems do you think there are still unsolved problems in CPCs testing, and what are the research directions of CPCs detection in the future?

At present, the biggest problem with CPCs is that there is no uniform flow inspection specification in the world, so there is no uniform cut-off value
.
The definition of cut-off values varies from study to study, including our studies and the definition of cut-off values from international studies
.
Secondly, improving the positive rate of CPCs detection is also a very important issue
.
Most of the research centers use different panels and the number of cells set, the positive rate is very different, the positive rate of different research centers varies from 50% to 100%, if the detection method is sensitive, the CPCs positive rate can reach 100%.

The future research direction has the following aspects: (1) to achieve unified standardized detection of CPCs; (2) Explore the application value
of CPCs in SMM prognosis judgment and follow-up.
Because the future is very important
for the identification of SMMs, especially high-risk SMMs.
If the detection of CPCs can be combined into the prognostic judgment of SMM, it is also of great significance for the identification of high-risk SMMs; (3) How to combine CPCs in active MM with the existing prognostic judgment system to further refine patient stratification, including how to replace bone puncture at some nodes, or how to combine calcaneal puncture more effectively for more accurate efficacy judgment; (4) Explore the application
of CPC cs in MM maintenance therapy and follow-up.

Professor Sun Chunyan

• Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

• Grade III professor, chief physician, doctoral supervisor

• Member of the Standing Committee of the Hematology and Oncology Professional Committee of the Chinese Anti-Cancer Association

• Young member of the Hematology Branch of the Chinese Medical Association

• He is a member of the Experimental Diagnostics Group of the Hematology Branch of the Chinese Medical Association

• He is a member of the Plasma Cytology Group of the Hematology Branch of the Chinese Medical Association

• He is a member of the Blood Disease Transformation Committee of the Chinese Anti-Cancer Association

• Deputy Leader of the Chinese Fahrenheit Macroglobulinemia Working Group

• Member of the Standing Committee of the Hematology Professional Committee of the Chinese Medical Education Association

• Vice Chairman of Myeloma Branch of China Medical Education Association

• Chairman of the Translational Medicine Professional Committee of Hubei Medical Bioimmunology Society

• Chairman of the Youth Committee of the Hematology Professional Committee of Wuhan Medical Association

• Corresponding editorial board member of Chinese Journal of Hematology

• He has presided over 5 projects of the National Natural Science Foundation of China

• He has published more than 110 papers and more than 60 SCI papers in authoritative journals at home and abroad

• In 2007, 2012 and 2020, he won the first prize of Hubei Provincial Science and Technology Progress Award

Poke "Read the original article" to see more