Sonrotoclax and BCMA Bispecific Antibody in Newly Diagnosed Systemic AL Amyloidosis Based on t(11;14) Genetic Stratification

This study is a prospective, single-center, phase Ib/II clinical trial designed to evaluate the tolerability of sonrotoclax plus dexamethasone in this phase Ib/II umbrella study and to determine the recommended phase II dose (RP2D). It also aims to assess the safety and hematologic response rate of sonrotoclax plus dexamethasone in patients with newly diagnosed systemic light-chain amyloidosis (NDAL) harboring t(11;14), and of a BCMA/CD3 bispecific antibody in patients with NDAL without t(11;14). In addition, this study seeks to explore a chemotherapy-free treatment strategy based on t(11;14)-guided genetic stratification.

Inclusion Criteria: * Able to understand and voluntarily sign the informed consent form (ICF). * Age ≥18 years and ≤70 years. * Confirmed diagnosis of primary light-chain amyloidosis, according to the diagnostic and treatment guidelines for primary light-chain amyloidosis, 2021 revised edition. 1. Subjects entering the phase Ib dose-escalation stage must also have confirmed t(11;14) translocation by FISH or other genetic testing. Newly diagnosed systemic AL amyloidosis, with no prior systemic anti-tumor therapy for AL amyloidosis. * Measurable disease at screening, defined as: a) Difference between involved and uninvolved serum free light chains (dFLC) \>20 mg/L. * Eastern Cooperative Oncology Group (ECOG) performance status ≤3. * Adequate hepatic function, defined as total bilirubin \8500 ng/L; 3. Congestive heart failure with hospitalization for cardiovascular disease within 4 weeks before randomization; 4. Heart failure judged by the investigator to be caused by ischemic heart disease, such as prior myocardial infarction with elevated cardiac enzymes and electrocardiographic changes, or uncorrected valvular disease, rather than AL amyloid cardiomyopathy; 5. History of sustained ventricular tachycardia or ventricular fibrillation, or history of atrioventricular (AV) node or sinoatrial (SA) node dysfunction requiring a pacemaker or implantable cardioverter-defibrillator (ICD) but without implantation. Patients with an implanted pacemaker or ICD may be enrolled; 6. Corrected QT interval using Fridericia's formula (QTcF) \>500 msec. Patients with an implanted pacemaker may be enrolled regardless of the corrected QT interval result; 7. Supine systolic blood pressure \