Personalized tracking of M proteins, EasyM advances precision medicine practices in myeloma

Multiple myeloma accounts for 1% of all tumors, is the world's second largest hematological tumor, its global incidence is as high as 1.
78/100,000 people, the five-year survival rate of myeloma patients in China is about 24.
8%, Japan is 33.
3%, and the United States is 46.
7% [1], and the cure rate of myeloma is extremely low, the recurrence rate is as high as 28%, therefore, the development of efficient and sensitive detection methods is of great significance
for the treatment and prognosis of multiple myeloma.

Figure 1.
Global incidence of multiple myeloma[1]

Minimal residual disease (MRD) is currently commonly used clinically to evaluate
the development of multiple myeloma.
Minimal residual disease (MRD) is essential for assessing the extent of remission in multiple myeloma, and multiple studies have demonstrated that achieving MRD-negative is associated with improved survival outcomes and can serve as an alternative treatment endpoint for progression-free survival (PFS) and overall survival (OS), but the optimal timing for MRD assessment remains to be determined
.
Common techniques for detecting MRD include next-generation flow cytometry (NGF), next-generation sequencing (NGS), positron emission tomography-X-ray computed tomography/magnetic resonance imaging (PET-CT/MRI), and mass spectrometry to detect -M proteins
。 Among them, NGS, as an emerging MRD detection method, can detect the change of NGS-panel burden of a variety of tumor-related gene mutations at one time, and comprehensively evaluate the factors of tumor subcloning, emerging clone and clonal hematopoiesis, but the sensitivity of ordinary NGS technology is only about 2%, resulting in its accuracy is slightly insufficient
。 NGF technology overcomes the shortcomings of low sensitivity and lack of unified standards of traditional detection technology, and has the advantages of wide applicability, rapid and simple detection, but due to the large data output of NGF instruments, it has high requirements for computer equipment.
At the same time, the operation process of the experimental process and the interpretation of the data largely depend on the professional level of the technician; Its high requirements for the quality and quantity of samples limit the promotion and application
of this technology in clinical testing.
Although imaging detection techniques such as PET-CT/MRI can assess tumor residue throughout the body at one time, they have great advantages
for timely detection of distant tumor metastasis.
However, the drawback
of low sensitivity remains.
Based on the advantages and disadvantages of the above technology, mass spectrometry detection of M protein is increasingly used in clinical practice due to its rapid, accurate and high sensitivity technical advantages
.
M protein is a monoclonal proliferation of plasma cells and their secreted monoclonal globulin, which is the main role molecule
in the complex clinical manifestations of multiple myeloma.
However, in these two important multiple myeloma tests, patients with myeloma are often found to be MRD-negative but still positive for serum M protein (a complete response to myeloma treatment is defined as a complete removal of M protein from the blood after intensive therapy).

Therefore, the quantitative detection of M protein is clinically important for the diagnosis of multiple myeloma[2].

Figure 2.
The importance of
MRD testing.
The importance of
MRD testing is demonstrated by comparing before and after MRD testing for treatment and prognostic recurrence.

At present, the commonly used methods for the determination of M protein include serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) techniques
.
Serum protein electrophoresis is widely used in clinical trials to detect abnormal proteins
in samples.
Serum protein electrophoresis can be used to detect M protein, but for acute acute reactive protein or lipoprotein in α2 or β region caused by peak type and M peak, such as most nephropathy, glomerulonephritis patients α2 or β area appear high sharp peaks, serum protein electrophoresis can not directly identify it as M protein, need to be further confirmed
by immunofixation electrophoresis.
Immunofixation electrophoresis (IFE) technique is an immunological analysis method combining zonal electrophoresis with specific antiserum immunoprecipitation reaction, and is the most commonly used method
for clinical identification of M protein.
Immunofixation electrophoresis has significant advantages in rapid isolation and identification of M proteins, and can type M proteins, which is faster, simpler and more accurate than bone marrow cell morphology and serum protein electrophoresis
.
However, both methods are high in terms of sampling, detection and accuracy, as well as the quality of personnel, and it is difficult to adapt to today's clinical requirements
that require rapid and accurate diagnosis.
In addition, the M protein sequence is individualized, so true personalized monitoring can only be achieved by obtaining its sequence by protein sequencing, which is not available
for either method.

Figure 3.
Serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) techniques[3]

In view of the problems existing in the rapid and accurate clinical detection of M protein, Shanghai Fast Sequence Bio published a report on "Based on Mass Spectrometry Technology
.
At the same time, combined with its years of technical accumulation in the field of protein detection, EasyM multiple myeloma blood test technology
has been developed.

The EasyM multiple myeloma blood test is divided into two stages
: M protein sequencing and personalized monitoring.

The first stage: protein mass spectrometry was used to sequence the M protein in the serum of patients with MM in the diagnostic stage, and the full-length sequence of the amino acid of the M protein could be determined on the protein sequencing platform of Shanghai Express with only 100 microliters
.

Step 2: Personalized monitoring, after completing the first step to obtain the patient's individual specific M protein sequence information, Fast Sequence Bio can accurately quantify the serum M protein of patients at all stages of the disease course through targeted proteomics, track its concentration changes, and realize the monitoring
of the disease.

Figure 4.
EasyM Step 1: M protein sequencing; Step 2: Personalized monitoring

The technology has the advantages
of high sensitivity, non-invasiveness and personalization.

High sensitivity: EasyM is 200-1000 times more sensitive than the existing clinical blood test methods SPEP and IFE, which can detect myeloma recurrence about half a year in advance and avoid false negatives
caused by bone marrow aspiration sampling location deviation 。 In a research article titled "A Personalized Mass Spectrometry–Based Assay to Monitor M-Protein in Patients with Multiple Myeloma (EasyM)," published in September 2021 in CLINICAL CANCER RESEARCH, the top journal of cancer research, researchers used EasyM to participate in the study The results of 26 patients in the MCRN-001 clinical trial showed that EasyM increased the detection sensitivity of M protein in patients (detection of M protein at 0.
58 mg/L) by a factor of 1,000 and 200 times, respectively, compared to serum protein electrophoresis and immunofixation electrophoresis, reaffirming that EasyM, a non-invasive, sensitive detection method, has excellent performance compared to other detection methods and is expected to be ideal for multiple myeloma surveillance and recurrence prediction in the future [5]
。

Non-invasive: In addition, bone marrow aspiration detection methods are inconvenient for frequent sampling and cause patient distress, EasyM uses non-invasive blood sampling for easy routine testing, requiring only 50-100 microliters of blood to monitor disease status
as needed 。 In July 2021, an article entitled "Mass Spectrometry Provides a Highly Sensitive NoninvasiveMeans of Sequencing and Tracking M-Protein in the Blood of Multiple" was published in the Journal of Proteome Research In the MyelomaPatients' research article, researchers used EasyM to test serum for M protein in 12 samples
.
The results showed that EasyM required only 50 μL of serum compared to conventional ctDNA testing, requiring a smaller sample size, which greatly improved the accuracy and non-invasive nature of the noninvasive test in patients with multiple myeloma [6].

Personalization: Finally, the EasyM test tracks the individual patient-specific M protein, so each test is tailored to the patient without sample bias, enabling truly personalized precision medicine
.

Through EasyM multiple myeloma blood test technology, Shanghai Fast Biotech can complete personalized monitoring within 3-5 days and accurate diagnosis
in 2-3 weeks.
It provides a reference for the formulation of the next precise treatment plan for patients with multiple myeloma, and protects the life and health
of patients.

Fast Bio's de novo sequencing technology deeply integrates mass spectrometry technology and computer AI algorithm, relying on its advanced antibody sequencing technology, taking the detection of Minimal Residual Disease (MRD) of Multiple Myeloma (MM) as a breakthrough, actively promoting the development of domestic clinical protein profiling technology, and is committed to promoting the continuous upgrading of the current clinical detection technology and methods of multiple myeloma.
In order to allow every clinical patient to benefit
from the technological upgrade of Fast Biologics.

References:

[1]

[2] Marion al.
Early achievement of measurable residual disease negativity in the treatment of multiple myeloma as predictor of outcome.
Br J Haematol .
2022 Mar 11.
doi: 10.
1111/bjh.
18103.

[3] Jung D, Jain P, Yao Y, Wang M.
Advances in the assessment of minimal residual disease in mantle cell lymphoma.
J Hematol Oncol.
2020 Sep 24; 13(1):127.
doi: 10.
1186/s13045-020-00961-8.

[4] Liu GY, Tang O, Brotman DJ, Miller ER 3rd, Moliterno AR, Juraschek SP.
Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy.
PLoS One.
2020 Jan 15; 15(1):e0224977.

[5].
Liyasova M, McDonald Z,Taylor P, et al.
A personalized mass spectrometry-based assay to monitorM-protein in multiple myeloma patients (EasyM)[J].
Clinical Cancer Research,2021.