The goal of this study is to evaluate the efficacy and safety of Sonrotoclax combined Regimen in patients with t(11;14) AL amyloidosis. Participants will receive the Sonrotoclax Plus Dexamethasone regimen with or without Daratumumab for 12 cycles. The Hematologic Response, Organ Response, Survival, and Safety will be evaluated.
Patients who meet the diagnostic criteria for Primary Systemic Light Chain Amyloidosis (according to the Systemic Light Chain Amyloidosis Diagnosis and Treatment Guidelines (2021 Revision)).
Age ≥ 18 years.
Confirmed FISH test result of t(11;14) positive by each center or a third-party laboratory, or a prior FISH test report indicating t(11;14) positivity
ECOG Performance Status score of 0-2.
Meets the diagnostic criteria for active multiple myeloma or active lymphoplasmacytic lymphoma
Presence of other malignancies at an advanced stage with systemic metastases.
IgM-type AL amyloidosis.
Prior treatment with a BCL-2 inhibitor (BCL-2i).
Single group
sonrotoclax
Drugcohor A \& Cohort B: Induction therapy (C1-4) : Sonrotoclax once daily A conventional 3+3 design will determine the target sonrotoclax dose during the C1 safety run-in phase. And dose-limiting toxicity (DLT) assessed during a 28-day evaluation window. Patients who are enrolled after the safety run-in phase will receive sonrotoclax at the dose determined in safety run-in phase. A 3-day ramp-up is used (320 mg: 80→160→320 mg on D1-D3; 640 mg: 160→320→640 mg on D1-D3) in C1, with the Day 3 dose maintained from Day 4 onward for all patients. Subsequent therapy (C5-12) Sonrotoclax once daily (same dose as in the induction phase)
Daratumumab
DrugCohor A Only Daratumumab (16 mg/kg intravenously) or daratumumab and hyaluronidase-fihj (1800 mg subcutaneously）once weekly C1-2; every two weeks C3-6; every month C7-12
Dexamethasone
Drugcohor A \& Cohort B: Dexamethasone (40 mg, once weekly) for 12 cycles. The dose was halved for patients 75 years of age or older, and in patients who were intolerant of dexamethasone, as judged by the investigators.
hematological ≥VGPR rate within four cycles of induction therapy
Defined as the proportion of patients achieving VGPR, or CR within four cycles of therapy
Hematological ORR after four cycles of therapy
Defined as the proportion of patients achieving PR,VGPR, or CR at the end of four cycles of therapy
Hematological CR rate at the end of four cycles of therapy
Defined as the proportion of patients achieving CR at the end of four cycles of therapy
Cardiac response rate at the end of 6 cycles of treatment
Defined as the proportion of patients achieving Cardiac response at the end of 6 cycles of therapy
Hepatic response rate at the end of 6 cycles of treatment
Defined as the proportion of patients achieving Hepatic response at the end of 6 cycles of therapy
MRD negativity rate in patients achieving hematological CR
Defined as the MRD negativity rate in patients achieving hematological CR
MRD negativity rate
Defined as the proportion of patients achieving MRD negativity
Correlation analysis between different MRD status groups and MOD-PFS, PFS and OS
Correlation analysis between different MRD status groups and 1-year MOD-PFS, 1-year PFS and 1-year OS
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