Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease

Korábbi kezelés

• Prior exposure to both BCMA- and GPRC5D-targeted therapies (patients who have received only one of these targeted therapies are eligible for enrollment).

Más betegség

• Infectious diseases (e.g., HIV, active tuberculosis, etc.).
• Active hepatitis B or hepatitis C infection.
• Mental or psychological disorders preventing compliance with treatment or treatment evaluation.
• Severe allergic constitution or severe allergic history, particularly to aponermin, carfilzomib, thalidomide, dexamethasone or other effective components or excipients of related drugs.
• Significant dysfunction of major organs, such as the heart, lungs, or brain.
• Patients with severe autoimmune diseases. 11) Any other reasons deemed unsuitable for participation in this study as determined by the investigator.

Egyéb

• Plasma cell leukemia or solitary plasmacytoma.
• Evidence of primary or secondary resistance to elotuzumab, carfilzomib, or thalidomide.
• Pregnant or breastfeeding women, or women with pregnancy plans within the next six months.
• Abnormal vital signs or inability to cooperate with examinations.

• Be informed and voluntarily sign the Informed Consent Form (ICF).
• Age ≥18 years.
• Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
• Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 1 prior lines of therapy. Extramedullary disease (EMD) is defined as soft-tissue plasmacytomas NOT arising from skeletal lesions. The maximum diameter of extramedullary lesions should ≥2cm detected by physical exam and confirmed (when required) by Weight Bearing CT/MRI/PET-CT and/or biopsy.
• ECOG score is ≤ 2
• No active infections.
• Negative for HBV-DNA, HCV-RNA, and HIV.
• Liver function meeting the following criteria: Total bilirubin <1.5 × ULN (patients with Gilbert's syndrome must have total bilirubin <3 × ULN), ALT and AST <3 × ULN.
• Renal function meeting the following criteria: Creatinine clearance ≥30mL/min (calculated using the Cockcroft-Gault formula).
• Blood tests conducted within 7 days before screening must meet the following standards: WBC count ≥1.0×10⁹/L, Hemoglobin ≥70g/L, Platelet count ≥75×10⁹/L or ≥50×10⁹/L (if ≥50% plasma cells are present in bone marrow); Or as determined appropriate by the investigator.
• Patients receiving hematopoietic growth factors (e.g., erythropoietin, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and platelet-stimulating factors such as thrombopoietin [TPO] or interleukin-11) must stop such treatments at least 2 weeks prior to screening.
• Non-pregnant female patients must confirm pregnancy negativity at screening (via β-hCG serum test or urine pregnancy test).
• Male patients, female patients of childbearing potential, and their partners must agree to use effective contraception during the treatment period and for at least 3 months after CAR-T cell infusion.
• Male patients must agree not to donate sperm, starting from the initial screening period until 90 days after the last dose.
• Patients must agree to comply with study procedures and follow-up visits.