QLS4131 for Relapsed/Refractory Multiple Myeloma With Extramedullary Disease

1. Participants who are aware of and voluntarily sign the informed consent form (ICF), aged ≥18 years at the time of signing the ICF; male or female.

2. ECOG performance status of 0-2. 3. Diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) criteria, and meeting the following criteria:

1. Received at least 1 line of systemic anti-myeloma therapy, previously exposed to proteasome inhibitors (PI), immunomodulatory drugs (IMiD), and anti-CD38 monoclonal antibodies, and refractory to the most recent line of therapy or progressed within the specified time after completion of the most recent line of therapy;

2. Extramedullary disease identified by imaging examination, including the following two categories:

   1. True extramedullary disease (true EMD): soft tissue or organ plasmacytoma not contiguous with bone, with at least one lesion measuring ≥2 cm in the longest diameter;

   2. Paraskeletal disease (PSD): lesions formed by extension of bone lesions through the cortical bone into adjacent soft tissue, with at least one lesion measuring ≥5 cm in the longest diameter, or more than 2 paraskeletal lesions measuring ≥2 cm in the longest diameter.

      4. Participants who have previously received CAR-T cell therapy or bispecific antibody therapy are allowed. For participants who have previously received BCMA- or GPRC5D-targeted therapy, prior targeted therapy must involve only one of the targets, BCMA or GPRC5D. The interval from CAR-T cell infusion to the first administration of study drug must be ≥3 months, and the interval from the last dose of bispecific antibody to the first administration of study drug must be ≥28 days.

      5. Participants without measurable hematologic disease are allowed to enroll. Measurable hematologic disease is defined as meeting any one or more of the following criteria:

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   1. Serum M protein level ≥1.0 g/dL;
   2. Urine M protein level ≥200 mg/24 hours;

   3. Serum free light chain level ≥10 mg/dL with an abnormal serum free light chain ratio.

      6. Adequate organ function. 7. Participants must voluntarily participate and be able to complete the study procedures and follow-up examinations.

Exclusion Criteria:

1. Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or primary/secondary plasma cell leukemia.
2. Central nervous system involvement or clinical evidence of meningeal involvement.
3. Previous treatment with simultaneous BCMA and GPRC5D targeting therapies, including separate treatment targeting BCMA and GPRC5D, or treatment with dual-target BCMA and GPRC5D therapies.
4. Radiotherapy: In principle, participants should not have received radiotherapy within 3 months before enrollment. If the lesion has previously received radiotherapy, radiographic evidence of clear progression after radiotherapy is required before it can be considered a baseline target lesion.
5. Severe and/or uncontrolled cardiac disease.
6. Major surgery within 4 weeks before the first administration of study drug, or planned major surgery during the study period.
7. Active infection, including HIV infection, active hepatitis B (HBV-DNA positive), active hepatitis C (HCV-RNA positive), active or latent syphilis, active tuberculosis, or other active infections considered unsuitable by the investigator.
8. Concurrent other malignancies; or serious concomitant diseases that, in the investigator's assessment, seriously threaten participant safety or affect completion of the study.
9. Pregnant or breastfeeding women.
10. History of severe allergy or hypersensitivity to study drug components.
11. Any other conditions that, in the investigator's judgment, make the participant unsuitable for enrollment.