Method for detecting effectiveness of lenalidomide of multiple myeloma patient

Abstract

The invention relates to the field of medical treatment, and discloses a method for detecting whether lenalidomide of a patient with multiple myeloma is effective or not. The method comprises the following steps: treating in-vitro bone marrow mononuclear cells of a subject by using lenalidomide, and respectively detecting the proportion of CD138 + cells and the IKZF1 / 3 expression quantity in cells of a lenalidomide treatment group and an untreated group. The method objectively reflects whether relapse and progression MM patients are resistant to the lenalidomide, if the patients are resistant to the lenalidomide, the patients are replaced with substituted chemotherapeutic drugs such as the lenalidomide and pomalidomide, and if the patients are not resistant to the lenalidomide, the patients are replaced with other chemotherapeutic drugs in the scheme. A theoretical basis is provided for replacing chemotherapeutic drugs for the MM patient, clinical medication is guided, invalid treatment is avoided through precise treatment, and the economic burden of the patient is relieved.

Description

Technical Field

[0001] The present application relates to the medical field, and more particularly, to a method for detecting whether lenalidomide is effective in patients with multiple myeloma. Background Art

[0002] Multiple myeloma (MM) is the second most common hematologic malignancy, with a recent increase in incidence. Combination chemotherapy regimens containing lenalidomide are currently the most commonly used chemotherapy regimen for MM. However, patients can develop drug resistance after using lenalidomide and other chemotherapy drugs.

[0003] In the treatment of MM patients, if the disease relapses or progresses, clinicians will assume that the patient is resistant to the combination chemotherapy regimen and, if resistance occurs, will switch to the resistant drug. However, determining which drug is resistant often depends on the clinician's clinical experience. For example, the most commonly used chemotherapy regimen for MM patients is bortezomib + lenalidomide + dexamethasone. If bortezomib resistance is determined, bortezomib is replaced with ixazomib; if lenalidomide resistance is determined, lenalidomide is replaced with pomalidomide. However, this method requires a high level of clinical experience from the physician, lacks objective evidence, and has low accuracy. Inaccurate judgments can sometimes even delay the patient's disease treatment.

[0004] Currently, there is no clinical technology for detecting whether MM patients are resistant to lenalidomide. Summary of the Invention

[0005] The purpose of the invention of this application is to provide a method for detecting whether lenalidomide is effective in patients with multiple myeloma.

[0006] In order to achieve the above-mentioned invention objectives, this application adopts the following technical solutions:

[0007] In the first aspect, the present application provides a method for detecting whether lenalidomide is effective in patients with multiple myeloma, comprising the steps of treating the subject's isolated bone marrow mononuclear cells with lenalidomide, and respectively detecting the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the lenalidomide-treated group and the untreated group.

[0008] Furthermore, in the step, flow cytometry is used to detect the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the cells.

[0009] Furthermore, in the above step, the following judgment is made based on the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the cells:

[0010] Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group decreased significantly, indicating that the subjects were very sensitive to lenalidomide;

[0011] Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group did not change significantly, while the expression of IKZF1 and / or IKZF13 decreased significantly, indicating that the subject is sensitive to lenalidomide;

[0012] Compared with the untreated group, there was no significant change in the proportion of CD138+ cells and IKZF1 / 3 expression in the lenalidomide-treated group, indicating that the subjects were resistant to lenalidomide.

[0013] Furthermore, the lenalidomide-treated group refers to bone marrow mononuclear cells cultured with 50 nM lenalidomide for 24 hours; the untreated group refers to bone marrow mononuclear cells cultured with an equal volume of DMSO for 24 hours.

[0014] Furthermore, the method for detecting whether lenalidomide is effective in multiple myeloma patients comprises the following steps:

[0015] Step 1: After the subject relapses or disease progresses, a bone marrow puncture is performed, and 3 ml of the patient's bone marrow fluid is collected and subjected to density gradient centrifugation to separate the patient's bone marrow mononuclear cells;

[0016] Step 2: Bone marrow mononuclear cells of the subjects were cultured in vitro and divided into two groups: the lenalidomide-treated group was treated with 50 nM lenalidomide for 24 hours, and the untreated group was treated with an equal volume of DMSO for 24 hours;

[0017] Step 3, collecting the cultured cells for CD138 and IKZF1 / 3 flow cytometry detection;

[0018] Step 4, result analysis:

[0019] Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group decreased significantly, indicating that the subjects were very sensitive to lenalidomide;

[0020] Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group did not change significantly, while the expression of IKZF1 and / or IKZF13 decreased significantly, indicating that the subject is sensitive to lenalidomide;

[0021] Compared with the untreated group, there was no significant change in the proportion of CD138+ cells and IKZF1 / 3 expression in the lenalidomide-treated group, indicating that the subjects were resistant to lenalidomide.

[0022] In a second aspect, the present application provides a system for detecting whether a multiple myeloma patient has lenalidomide resistance, comprising:

[0023] The data acquisition module is used to collect the CD138+ cell ratio and IKZF1 / 3 expression level in the subjects' in vitro bone marrow mononuclear cells, between the lenalidomide-treated group and the untreated group.

[0024] Furthermore, the system further includes:

[0025] The data processing module compares whether the proportion of CD138+ cells in the lenalidomide-treated group and the untreated group has changed. If the proportion of CD138+ cells in the lenalidomide-treated group is significantly decreased compared to the untreated group, the output is result 1: the subject is very sensitive to lenalidomide.

[0026] If the proportion of CD138+ cells in the lenalidomide-treated group does not change significantly compared to the untreated group, then compare whether the expression of IKZF1 / 3 in the lenalidomide-treated and untreated groups changes. If the expression of IKZF1 and / or IKZF13 in the lenalidomide-treated group is significantly decreased compared to the untreated group, then output result 2: the subject is sensitive to lenalidomide.

[0027] Otherwise, output result 3: the subject is resistant to lenalidomide.

[0028] Furthermore, the system further includes:

[0029] The data output module is used to output the results 1, 2, and 3.

[0030] In a third aspect, the present application provides a device for detecting whether multiple myeloma patients have resistance to lenalidomide. The device includes a memory and a processor. The memory stores a program. When the processor executes the program, it implements any one of the above methods for detecting whether lenalidomide is effective in multiple myeloma patients.

[0031] In a fourth aspect, the present application provides a computer-readable storage medium, characterized in that the computer-readable storage medium includes instructions, which, when executed, enable the computer to execute any one of the above methods for detecting whether lenalidomide is effective in patients with multiple myeloma.

[0032] In summary, this application has the following beneficial effects:

[0033] The method of this application objectively reflects whether patients with relapsed or progressive MM are resistant to lenalidomide. If resistant, alternative chemotherapy drugs such as lenalidomide and pomalidomide are used. If not, other chemotherapy drugs in the regimen are used instead. This provides a theoretical basis for switching chemotherapy drugs for MM patients, guides clinical medication use, ensures precise treatment, avoids ineffective treatment, and reduces the financial burden on patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 : CD138+ cell ratio results of patients in Example 1;

[0035] Figure 2 : The expression results of IKZF1 and IKZF3 in the patient in Example 1;

[0036] Figure 3 : CD138+ cell ratio results of patients in Example 2;

[0037] Figure 4 : The expression results of IKZF1 and IKZF3 in the patient in Example 2;

[0038] Figure 5 : CD138+ cell ratio results of patients in Example 3. DETAILED DESCRIPTION

[0039] The technical solutions and effects of the present application are further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the invention, rather than to limit the invention.

[0040] The present application discloses a method for detecting whether lenalidomide is effective in patients with multiple myeloma. Lenalidomide is applied in vitro to the patient's bone marrow mononuclear cells to detect whether the proportion of CD138+ cells and the expression of lenalidomide downstream molecules IKZF1 / 3 are decreased, thereby determining whether the patient is resistant to lenalidomide.

[0041] Principle of the test: Fluorescently labeled antibodies react with the cell suspension to be tested. The antibodies specifically bind to CD molecules on the cell membrane surface, forming a fluorescent antibody-cell complex. The fluorescence level and expression of the labeled fluorescent cells are measured by flow cytometry.

[0042] 1. Specimen

[0043] 1.1 Original specimen type: Bone marrow. Clinically, bone marrow puncture is performed after relapse or disease progression, and 3-5 ml of bone marrow fluid is collected.

[0044] 1.2 Sample volume: Bone marrow: 3-5 ml, which can be adjusted appropriately according to the patient's cell count.

[0045] 1.3 Specimen collection container: K2EDTA anticoagulant vacuum collection tube.

[0046] 1.4 Sample stability requirements and storage:

[0047] 1.4.1 No clots. If there are clots, the specimen must be tested and this should be noted in the test report;

[0048] 1.4.2 Specimens should be submitted for testing within 4 hours of collection; placed at room temperature (18-25°C) and tested within 6 hours. After testing, specimens should be refrigerated at 2-8°C for one week.

[0049] 1.5 In vitro culture of samples:

[0050] 1.5.1 Isolate the patient's bone marrow mononuclear cells using density gradient centrifugation (Ficoll method);

[0051] 1.5.2 Patient bone marrow mononuclear cells were cultured in vitro and divided into two groups: the drug group was treated with 50 nM lenalidomide for 24 hours, and the control group was treated with an equal volume of DMSO for 24 hours;

[0052] 1.5.3 Collect the cultured cells for further CD138 and IKZF1 / 3 flow cytometry detection.

[0053] 2. Reagents

[0054] 2.1IKZF3-PE, IKZF1-PE-cy7 (Biolegend, USA);

[0055] 2.2CD138-APC, CD45-KrO (Beckman Coulter, USA);

[0056] 2.3LIVE / DEAD Fixable Blue Dead Cell Stain Kit (Thermo Fisher Invitrogen Company);

[0057] 2.4PBS: Boster Biological, add 2 liters of water to dissolve, adjust the pH value to 7.2-7.6, valid for half a year.

[0058] 2.5 Membrane rupture and redness splitting solution: BD Pharmingen, BD Company, USA, valid until the expiration date marked on the reagent.

[0059] 2.6 Packaging specifications: Antibodies: PE (6 μg / mL, 125 μL), PE-Cy7 (6 μg / mL, 125 μL), APC (100 μg / mL, 0.5 mL), KrO (50 μg / mL, 1 mL).

[0060] 2.7 Reagent Usage: Liquid or antibody reagents can be used directly after preparation.

[0061] 2.8 Reagent Storage Conditions: Fluorescent antibodies should be stored in a refrigerator at 2-8°C, away from light. Unopened Beckman antibodies are valid until the expiration date marked on the reagent. Once opened, the reagent is stable for 90 days. BD Pharmingen antibodies should be stored in a refrigerator at 4°C, away from light. Once opened, the reagent should be used up within 6 months. PBS should be stored at room temperature and is stable for 9 days. Opened reagent bottles should be labeled with the date of opening.

[0062] 3. Detection process

[0063] 3.1 Steps before specimen testing:

[0064] 3.1.1 Count the nucleated cells of the specimens received and calculate the nucleated cell concentration in the specimens; the optimal nucleated cell concentration is approximately 5×10 6 cells / mL.

[0065] 3.1.2 Determine the number of test tubes required for each specimen, the test items in each tube, and the type of fluorescent antibody to be labeled. Mark the tubes with a marker. Currently, our laboratory has two tubes for lymphoma testing: 1) tube labeled with IKZF3-PE, IKZF1-PE Cy7, CD138-APC, LIVE / DEAD, and CD45-KrO; 2) tube labeled with the same type of antibody. Different colored antibodies may be used depending on clinical antibody usage.

[0066] 3.1.3 Prepare BD Pharmingen working solution.

[0067] 3.1.4 Filter 500-1000 μL of the sample to be tested through a 300-mesh nylon membrane, add 2 ml of PBS, suspend the cells, mix thoroughly, centrifuge at 400 g for 5 minutes, and discard the supernatant. Wash away any remaining culture medium and other components.

[0068] 3.1.5 According to the instructions of each antibody, add appropriate amount of CD138-APC, LIVE / DEAD, and CD45-KrO cell membrane fluorescent labeling antibodies, mix thoroughly, and incubate at room temperature in the dark for 15 minutes.

[0069] 3.1.6 Add 1 ml of 1x Fix / Perm to the above sample, suspend the cells, mix thoroughly, and incubate at 2-8°C in the dark for 40-50 minutes.

[0070] 3.1.7 Add 1 ml of 1x Perm / Wash, mix thoroughly, centrifuge at 400 g for 5 minutes, and discard the supernatant.

[0071] 3.1.8 Add 2 ml of 1x Perm / Wash, resuspend the cells, mix thoroughly, centrifuge at 400 g for 5 min, and discard the supernatant.

[0072] 3.1.9 According to the instructions of each antibody, add appropriate amount of various nuclear fluorescent labeled antibodies (IKZF3-PE, IKZF1-PE-cy7) and 80-100125μL Perm / Wash, mix well, and incubate at 2-8℃ for 40-50 minutes.

[0073] 3.1.10 Add 2 ml of Perm / Wash to the test tube, suspend the cells, mix thoroughly, centrifuge at 400 g for 5 minutes, discard the supernatant, and aspirate the remaining liquid at the top of the test tube to minimize cell loss.

[0074] 3.1.11 Add approximately 0.3 ml of PBS to each tube and test on the instrument.

[0075] 3.1.12 If the dyeing process cannot be started immediately (due to instrument failure, etc.), place the sample at 2-8°C in a dark place and test within 24 hours.

[0076] 3.2 Sample testing process:

[0077] 3.2.1 Before starting, fill the sheath fluid and cleaning fluid and empty the waste liquid bucket;

[0078] 3.2.2 Turn on the computer, open the flow chamber door, turn on the flow cytometer host, start the Navios software and enter the operator name and password. After the laser stabilizes for half an hour, perform the test.

[0079] 3.2.3 Sample Testing: Drag out the panel and enter the Carousel No. in the Worklist Manager, the patient's name in the "Sample ID1" column, and the date in the "Sample ID2" column. Acquire 250,000 nucleated cells. Adjust the voltages of various parameters to clearly separate the cell populations. Compensation can be adjusted during analysis.

[0080] 3.2.4 Instrument maintenance: If there is no subsequent testing after sample loading, the machine must be maintained as required.

[0081] 4. Result analysis and reporting

[0082] 4.1 Analysis of results: Use relevant flow cytometry analysis software (such as Kaluza software, FlowJo software, etc.) and set gates based on clinical needs. The software automatically calculates the results. Set parameters based on fluorescent markers.

[0083] 4.2 Result evaluation: Analyze the proportion of CD138+ plasma cells in living cells and the expression of IKZF1 and IKZF3 in CD138+ plasma cells;

[0084] 4.3 Result analysis and reporting, see the following examples for details.

[0085] Example 1

[0086] (1) Patient information:

[0087] The patient, Song xx, is a 74-year-old male.

[0088] The patient was diagnosed with multiple myeloma over 5 years ago and had been under long-term follow-up in our department. During this follow-up, he was hospitalized in our department and a bone marrow aspiration and biopsy revealed recurrence of the disease.

[0089] (2) Cell extraction and culture

[0090] Three milliliters of bone marrow fluid was collected from the patient and isolated using density gradient centrifugation (Ficoll method). The mononuclear cells were cultured in vitro and divided into two groups: the drug-treated group was treated with 50 nM lenalidomide for 24 hours, and the control group was treated with an equal volume of DMSO for 24 hours. The cultured cells were collected and analyzed by flow cytometry for CD138 and IKZF1 / 3.

[0091] (3) Flow cytometry

[0092] ① First, look at the proportion of CD138+ cells (i.e. plasma cells), Figure 1 It can be seen that the proportion of CD138+ cells in the drug-added group did not decrease significantly;

[0093] ②Then look at the expression of IKZF1 and IKZF3 in CD138+ cells. Figure 2 It can be seen that there was no significant change in the expression of IKZF1 in the drug-added group, and the expression of IKZF3 in the cells decreased significantly after the addition of lenalidomide, indicating that the patients were still sensitive to lenalidomide.

[0094] Follow-up verification proved that the above results were effective.

[0095] Example 2

[0096] (1) Patient information

[0097] Patient Li xx, female, 65 years old.

[0098] The patient was diagnosed with multiple myeloma over a year ago and had been under long-term follow-up in our department. During this follow-up, he was hospitalized in our department and a bone marrow aspiration and biopsy revealed recurrence of the disease.

[0099] (2) Cell extraction and culture

[0100] Three milliliters of bone marrow fluid was collected from the patient and isolated using density gradient centrifugation (Ficoll method). The mononuclear cells were cultured in vitro and divided into two groups: the drug-treated group was treated with 50 nM lenalidomide for 24 hours, and the control group was treated with an equal volume of DMSO for 24 hours. The cultured cells were collected and analyzed by flow cytometry for CD138 and IKZF1 / 3.

[0101] (3) Flow cytometry

[0102] ① First, look at the proportion of CD138+ cells (i.e. plasma cells), Figure 3 It can be seen that the proportion of CD138+ cells in the drug-added group did not decrease significantly;

[0103] ②Then look at the expression of IKZF1 and IKZF3 in CD138+ cells. Figure 4It can be seen that there was no significant change in the expression of IKZF1 and IKZF3 in the drug-added group, suggesting that the patients were resistant to lenalidomide.

[0104] Follow-up verification proved that the above results were effective.

[0105] Example 3

[0106] (1) Patient information

[0107] Patient Li xx, male, 68 years old.

[0108] The patient was diagnosed with multiple myeloma over 2 years ago and had been under long-term follow-up in our department. During this follow-up, he was hospitalized in our department and a bone marrow aspiration and biopsy revealed recurrence of the disease.

[0109] (2) Cell extraction and culture

[0110] Three milliliters of bone marrow fluid was collected from the patient and isolated using density gradient centrifugation (Ficoll method). The mononuclear cells were cultured in vitro and divided into two groups: the drug-treated group was treated with 50 nM lenalidomide for 24 hours, and the control group was treated with an equal volume of DMSO for 24 hours. The cultured cells were collected and analyzed by flow cytometry for CD138 and IKZF1 / 3.

[0111] (3) Flow cytometry

[0112] Look at the proportion of CD138+ cells (i.e. plasma cells), Figure 5 It can be seen that the proportion of CD138+ cells in the drug-added group decreased significantly, indicating that the patients were very sensitive to lenalidomide.

[0113] Follow-up verification proved that the above results were effective.

[0114] In addition, 14 patients were further included for validation, as follows:

[0115] Case 1: Gong XX, newly diagnosed with MM, tested very sensitive according to the method of this application, and is currently in remission after treatment with a lenalidomide-containing regimen;

[0116] Case 2: Xia XX, terminal relapsed MM (had been treated with lenalidomide and pomalidomide for a long time), was found to be drug-resistant according to the method of this application;

[0117] Case 3: Li XX, a newly diagnosed MM, was found to be drug-resistant according to the method of this application and did not take lenalidomide again. The first-line regimen was Dara+BD, which was effective and the patient is currently in complete remission.

[0118] Case 4: Song XX, a patient with multiple relapsed MM, had been treated with lenalidomide and pomalidomide.

[0119] The patient was discontinued due to intolerance to the pomalidomide dose. The test was sensitive according to the method of this application, and the clinical trial of pomalidomide + pomalidomide sensitizer was added. The effect was significant. After one week of treatment, the abnormal plasma cell count dropped from 39% to 6%.

[0120] Case 5: Mao XX, MM relapsed after VRD treatment, tested sensitive according to the method of this application, remained unchanged with lenalidomide, and was switched from bortezomib to carfilzomib (KRD) after which the patient achieved remission;

[0121] Case 6, Wang XX, was lost to follow-up after one cycle of VRD and readmitted to the hospital 5 months later. The test was sensitive according to the method of this application. The patient's condition was not evaluated after treatment and was lost to follow-up again;

[0122] Case 7, Yan XX, relapsed MM, detected as drug-resistant according to the method of this application, and relieved after changing the drug treatment;

[0123] Case 8, Yu XX, relapsed after PD treatment and was found to be drug-resistant according to the method of this application;

[0124] Case 9, Jin XX, relapsed MM (previously treated with lenalidomide), detected as drug-resistant according to the method of this application;

[0125] Case 10, Zhai XX, relapsed MM (previously treated with lenalidomide), tested as resistant according to the method of this application, and sensitive to pomalidomide according to the method of this application, currently being treated with a pomalidomide-containing regimen;

[0126] Case 11, Yuan XX, newly diagnosed MM, tested sensitive according to the method of this application, and is currently in remission after VRD treatment;

[0127] Case 12, Xu XX, relapsed MM, tested sensitive according to the method of this application, and is currently in remission after continuing treatment with a lenalidomide-containing regimen;

[0128] Case 13, Liang XX, newly diagnosed with MM, tested sensitive according to the method of this application, and is currently in remission after continuing treatment with a lenalidomide-containing regimen;

[0129] Case 14, Cheng XX, was initially diagnosed with MM and tested sensitive according to the method of this application. He is currently being treated with a lenalidomide-containing regimen and has achieved relief.

[0130] Summarize:

[0131] 1. A total of 5 patients with newly diagnosed MM were included, of whom 4 were sensitive and responded to lenalidomide-containing regimens, and 1 was resistant and responded to lenalidomide-free regimens.

[0132] 2. There were 8 cases of recurrent MM, 3 of whom were still sensitive to lenalidomide (or pomalidomide) and continued to receive lenalidomide (or pomalidomide) and achieved remission after switching to other drugs that may be resistant to the drug; 5 cases were resistant to lenalidomide and achieved remission after switching to lenalidomide;

[0133] 3. One patient who tested sensitive was lost to follow-up.

[0134] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A method for detecting whether lenalidomide is effective in patients with multiple myeloma, characterized in that: The method includes the steps of treating the subject's isolated bone marrow mononuclear cells with lenalidomide, and detecting the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the lenalidomide-treated group and the untreated group.

2. The method for detecting whether lenalidomide is effective in multiple myeloma patients according to claim 1, characterized in that: In the step, flow cytometry is used to detect the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the cells.

3. The method for detecting whether lenalidomide is effective in multiple myeloma patients according to claim 1, characterized in that: In the above step, the following judgment is made based on the proportion of CD138+ cells and the expression level of IKZF1 / 3 in the cells: Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group decreased significantly, indicating that the subjects were very sensitive to lenalidomide; Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group did not change significantly, while the expression of IKZF1 and / or IKZF13 decreased significantly, indicating that the subject is sensitive to lenalidomide; Compared with the untreated group, there was no significant change in the proportion of CD138+ cells and IKZF1 / 3 expression in the lenalidomide-treated group, indicating that the subjects were resistant to lenalidomide.

4. The method for detecting whether lenalidomide is effective in multiple myeloma patients according to claim 1, wherein: The lenalidomide-treated group refers to bone marrow mononuclear cells cultured with 50 nM lenalidomide for 24 hours; the untreated group refers to bone marrow mononuclear cells cultured with an equal volume of DMSO for 24 hours.

5. The method for detecting whether lenalidomide is effective in multiple myeloma patients according to claim 1, characterized in that: The following steps are involved: Step 1: After the subject relapses or disease progresses, a bone marrow puncture is performed, and 3 ml of the patient's bone marrow fluid is collected and subjected to density gradient centrifugation to separate the patient's bone marrow mononuclear cells; Step 2: Bone marrow mononuclear cells of the subjects were cultured in vitro and divided into two groups: the lenalidomide-treated group was treated with 50 nM lenalidomide for 24 hours, and the untreated group was treated with an equal volume of DMSO for 24 hours; Step 3, collecting the cultured cells for CD138 and IKZF1 / 3 flow cytometry detection; Step 4, result analysis: Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group decreased significantly, indicating that the subjects were very sensitive to lenalidomide; Compared with the untreated group, the proportion of CD138+ cells in the lenalidomide-treated group did not change significantly, while the expression of IKZF1 and / or IKZF13 decreased significantly, indicating that the subject is sensitive to lenalidomide; Compared with the untreated group, there was no significant change in the proportion of CD138+ cells and IKZF1 / 3 expression in the lenalidomide-treated group, indicating that the subjects were resistant to lenalidomide.

6. A system for detecting whether a multiple myeloma patient has lenalidomide resistance, characterized in that: include: The data acquisition module is used to collect the CD138+ cell ratio and IKZF1 / 3 expression level in the subjects' in vitro bone marrow mononuclear cells, between the lenalidomide-treated group and the untreated group.

7. The system for detecting whether a multiple myeloma patient has lenalidomide resistance according to claim 6, characterized in that: Also includes: The data processing module compares whether the proportion of CD138+ cells in the lenalidomide-treated group and the untreated group has changed. If the proportion of CD138+ cells in the lenalidomide-treated group is significantly decreased compared to the untreated group, the output is result 1: the subject is very sensitive to lenalidomide. If the proportion of CD138+ cells in the lenalidomide-treated group does not change significantly compared to the untreated group, then compare whether the expression of IKZF1 / 3 in the lenalidomide-treated and untreated groups changes. If the expression of IKZF1 and / or IKZF13 in the lenalidomide-treated group is significantly decreased compared to the untreated group, then output result 2: the subject is sensitive to lenalidomide. Otherwise, output result 3: the subject is resistant to lenalidomide.

8. The system for detecting whether a multiple myeloma patient has lenalidomide resistance according to claim 7, characterized in that: Also includes: The data output module is used to output the results 1, 2, and 3.

9. A device for detecting whether a patient with multiple myeloma has resistance to lenalidomide, characterized in that: The device includes a memory and a processor, the memory stores a program, and when the processor executes the program, it implements the method for detecting whether lenalidomide is effective in multiple myeloma patients as described in any one of claims 1 to 5.

10. A computer-readable storage medium, characterized in that The computer-readable storage medium comprises instructions, which, when executed, cause the computer to perform the method for detecting whether lenalidomide is effective in a multiple myeloma patient according to any one of claims 1 to 5.

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