Inclusion Criteria:
1. Patients must meet all of the following inclusion criteria to be eligible for enrollment in this study:
2. Provide informed consent and voluntarily sign the informed consent form; Be male or female, aged ≥18 years;
3. Have relapsed or refractory multiple myeloma (RRMM) who have previously failed therapy with regimens containing at least one agent from each of the following three drug classes: proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies; i. Relapsed: Disease progression requiring salvage therapy after achieving a minimal response (MR) or better following prior anti-myeloma therapy; ii. Refractory: Lack of response (failure to achieve MR or better) during the last anti-myeloma therapy, or disease progression within 60 days after the last anti-myeloma therapy;
4. Before randomization, the investigator must pre-select a standard of care (SOC) treatment regimen based on the patient's disease status;
5. Have an ECOG performance status of 0-2;
6. Have at least one measurable disease parameter:
* Serum M-protein ≥5 g/L;
* Urine M-protein ≥200 mg/24 h;
* Serum free light chain (FLC) assay: involved FLC level ≥100 mg/L with an abnormal serum FLC ratio (\<0.26 or \>1.65);
7. Have organ function meeting the following requirements (no blood components or hematopoietic growth factors permitted within 7 days prior to first dose):
* Hematology: Absolute neutrophil count (ANC) ≥1.0×10⁹/L, hemoglobin ≥70 g/L, platelets ≥50×10⁹/L;
* Liver function: Total bilirubin ≤1.5×ULN, ALT ≤2.5×ULN, AST ≤2.5×ULN;
* Renal function: Creatinine clearance ≥30 mL/min;
8. All prior treatment-related toxicities (as defined by NCI CTCAE v6.0) must be ≤Grade 1 at screening, except for alopecia, non-clinically significant and asymptomatic Grade 2 laboratory abnormalities, and those parameters specifically permitted in the inclusion criteria;
9. Have an expected survival of ≥3 months.
Exclusion Criteria:
1. Central nervous system involvement or clinical symptoms of meningeal involvement by multiple myeloma;
2. Concomitant light chain amyloidosis, plasma cell leukemia, Waldenström macroglobulinemia, or POEMS syndrome;
3. History of any other malignancy within 3 years prior to first dose, except for malignancies with very low recurrence risk after curative treatment (e.g., squamous cell carcinoma or basal cell carcinoma of the skin, in situ cervical or breast cancer), or those who have undergone curative surgical resection (or other treatment) with no current evidence of disease and unlikely to impact survival during the study period;
4. Dysphagia or active gastrointestinal dysfunction that may impair drug absorption;
5. Evidence of cardiovascular risk, including any of the following:
* QTc interval: ≥450 ms in males, ≥470 ms in females (QT interval must be corrected for heart rate using Friderici's formula);
* Left ventricular ejection fraction (LVEF) \<50%;
* Electrocardiographic abnormalities deemed by the investigator to pose unacceptable risk, including clinically significant untreated or uncontrolled arrhythmias, second-degree (Mobitz II) or third-degree atrioventricular (AV) block;
* History of myocardial infarction, acute coronary syndrome (including unstable angina), coronary angioplasty, stent placement, or bypass surgery within 6 months prior to screening;
* Heart failure classified as NYHA Class III or IV;
* Uncontrolled severe hypertension (systolic blood pressure ≥170 mmHg or diastolic blood pressure ≥110 mmHg);
6. Active infection requiring antimicrobial, antiviral, or antifungal therapy (prophylactic therapy excluded):
* Oral antimicrobial therapy within 2 weeks prior to first dose;
* Intravenous antimicrobial therapy within 4 weeks prior to first dose;
* History of viral respiratory infection (e.g., COVID-19, influenza A or B) within 2 weeks prior to first dose;
7. Serological findings:
* HBsAg positive and/or HbcAb positive with HBV-DNA positive or above upper limit of normal (ULN); HCV antibody positive with HCV-RNA positive or above ULN;
* Active autoimmune disease, including HIV infection. Patients with well-controlled type 1 diabetes, euthyroid autoimmune thyroiditis, or skin diseases not requiring systemic therapy (e.g., vitiligo, psoriasis) are permitted;
* Active syphilis infection;
* Active tuberculosis (evidenced by chest imaging or other relevant testing within 3 months prior to screening or during screening; tuberculosis screening will be conducted per center protocol);
8. Received live or attenuated vaccine within 4 weeks prior to first dose;
9. Underwent major surgery within 4 weeks prior to first dose, or anticipated to undergo major surgery during the study period;
10. Received the following anti-myeloma therapies prior to first dose:
* Plasmapheresis within 28 days prior to first dose;
* Monoclonal antibody therapy within 21 days prior to first dose;
* Small molecule targeted therapy, cytotoxic chemotherapy, and/or proteasome inhibitor and/or other anti-tumor traditional Chinese medicine within 14 days or 5 half-lives (whichever is shorter) prior to first dose;
* Systemic corticosteroids (prednisone \>10 mg/day or equivalent dose) within 7 days prior to first dose;
* Autologous stem cell transplantation within 3 months prior to first dose;
* CAR-T or CAR-NK cell therapy within 3 months prior to first dose;
11. Previously received allogeneic stem cell transplantation;
12. Previously received BCMA-targeted therapy;
13. Plan to receive other anticancer therapy or investigational drugs during the study period;
14. Any severe and/or unstable pre-existing medical condition, psychiatric disorder, or other disease (including laboratory abnormalities) that may affect participant safety, informed consent acquisition, or adherence to study procedures;
15. Pregnant or lactating women; male participants (or their partners) or female participants who plan to become pregnant during the study or within 6 months after the last dose, and who are unwilling to use a medically accepted effective contraceptive method (e.g., intrauterine device or condom) during the study period;
16. Any patient deemed unsuitable for participation by the investigator..
SAT-specific exclusion criteria:
17. Inability to receive bortezomib as determined by the investigator;
18. Contraindication to bortezomib or history of life-threatening allergic reaction or intolerance (defined as drug-related AE leading to discontinuation of treatment);
19. Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy;
20. Received a strong CYP3A4 inducer within 5 half-lives prior to first dose;
21. Previously received pomalidomide or have a contraindication to pomalidomide (e.g., history of arterial or deep vein thrombosis within the past 3 months \[except intermuscular vein thrombosis\], contraindication to or unwillingness to receive prophylactic antithrombotic therapy as required by protocol), or life-threatening allergic reaction or intolerance to pomalidomide;
22. Previously received selinexor or have a contraindication to selinexor or life-threatening allergic reaction or intolerance to selinexor.
