A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL)
The goal of this clinical trial is to learn if teclistamab in combination with daratumumab (Tec-Dara) works to treat newly diagnosed multiple myeloma with concurrent light chain amyloidosis (MM+AL). It will also learn about the safety of this combination. The main questions it aims to answer are: Does Tec-Dara improve the 1-year progression-free survival rate compared to historical data (50% to 75%) in MM+AL patients? What are the rates of hematologic response (ORR, VGPR, CR, MRD negativity) and organ response in MM+AL patients treated with Tec-Dara? What medical problems do participants have when taking Tec-Dara? Participants will: Receive teclistamab subcutaneous injection with step-up dosing (0.06, 0.3, 1.5 mg/kg), followed by 1.5 mg/kg weekly in Cycle 1, 3.0 mg/kg every 2 weeks in Cycles 2-3, and 3.0 mg/kg every 4 weeks in Cycles 4-24 Receive daratumumab subcutaneous injection 1800 mg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks in Cycles 7-24 Continue treatment until disease progression, unacceptable toxicity, or a maximum of 24 cycles Undergo disease assessments every 28 days (±7 days) including laboratory tests for hematologic and organ response evaluation Provide bone marrow samples for MRD and RNA sequencing analysis
• Age ≥18 years, any sex/gender
• Diagnosis of multiple myeloma according to IMWG criteria
• Histopathologic diagnosis of AL amyloidosis confirmed by:
‣ Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following:
• Immunohistochemistry and/or immunofluorescence
∙ Mass spectrometry
∙ Electron microscopy/immunoelectron microscopy
• Measurable disease at screening
• Newly diagnosed, no prior anti-plasma cell therapy
• Adequate laboratory values:
‣ Hemoglobin ≥7.5 g/dL
⁃ Absolute neutrophil count ≥1.0×10⁹/L
⁃ Platelet count ≥70×10⁹/L (platelet transfusion acceptable; \>50×10⁹/L if ≥50% bone marrow nucleated cells are plasma cells)
⁃ ALT ≤2.5× upper limit of normal (ULN)
⁃ AST ≤2.5× ULN
⁃ Total bilirubin ≤2.0× ULN
⁃ Creatinine clearance ≥30 mL/min
⁃ Corrected serum calcium ≤14 mg/dL
• Male and female participants of childbearing potential must use at least 2 effective contraceptive methods during the study
• Voluntarily signed informed consent form (ICF)