Outcomes for patients with systemic light chain amyloidosis and Mayo stage 3B disease
Foteini Theodorakakou1, Alexandros Briasoulis1, Despina Fotiou1
1Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Insights
Novel regimens improve outcomes for high-risk cardiac amyloidosis patients. Early hematologic response is key, but cardiac response rates remain low, impacting overall survival in Mayo stage 3b disease.
Area of Science:
- Cardiology
- Hematology
- Oncology
Background:
- Cardiac light chain amyloidosis (AL) with Mayo stage 3b signifies a high-risk population with a poor prognosis.
- Novel therapeutic regimens are being investigated to improve outcomes in these patients.
Purpose of the Study:
- To evaluate treatment outcomes in patients with newly diagnosed AL amyloidosis and Mayo stage 3b disease who received novel regimens.
- To assess the impact of hematologic and cardiac response on overall survival.
Main Methods:
- Retrospective analysis of 80 consecutive patients with newly diagnosed AL amyloidosis and Mayo stage 3b disease.
- Evaluation of early mortality, hematologic response rates (CR, VGPR, PR), cardiac response rates, and overall survival.
- Analysis of factors associated with survival, including specific therapies (e.g., daratumumab-based) and clinical characteristics.
Main Results:
- Early mortality rate (<1 month) was 12.5%.
- Overall hematologic response rate was 40% (25% CR/VGPR, 15% PR).
- Daratumumab-based therapies showed high VGPR rates (52.6% at 1 month, 85.7% at 3 months).
- Cardiac response rates were 11.3% at 3 months and 18.8% at 6 months.
- Early hematologic response (at 1 and 3 months) and cardiac response (at 3 months) were associated with improved overall survival.
- Factors like kappa-light chain amyloidosis, peripheral nerve involvement, low systolic blood pressure, and advanced NYHA class were associated with poorer survival.
- Median overall survival was 6.3 months; patients receiving salvage therapy had a median OS of 24 months.
Conclusions:
- Patients with Mayo stage 3b cardiac amyloidosis benefit from early hematologic response with novel regimens.
- Despite improvements, cardiac response rates remain low, highlighting an unmet need.
- Achieving hematologic response is crucial for improving overall survival in this high-risk group.
Abstract:
Patients with cardiac light chain amyloidosis and Mayo stage 3b disease define a high-risk population with very poor prognosis. Here, we report treatment outcomes of 80 consecutive patients with newly diagnosed AL and Mayo 3b who received novel regimens. Early mortality (<1 month) rate was 12.5%. On intention-to-treat, overall hematologic response rate was 40%, with complete response (CR)/very good partial response (VGPR) in 25% and partial response (PR) in 15%. At 1- and 3- month landmark analysis CR or VGPR/PR rates were 25%/23.5% and 34%/25.5%, respectively. Among patients that were treated with daratumumab-based therapies, 52.6% and 85.7% achieved at least VGPR within one 1 and 3 months, respectively. Three-month cardiac response rate was 11.3% and 6-month was 18.8%. At least hemVGPR at 3 months was associated with cardiac response at 6 months (p = 0.034). Median overall survival (OS) was 6.3 months. At 1-month landmark at least hemPR was associated with better median OS (24.1 vs. 4.9 months, p = 0.017) and at 3-month landmark, at least hemVGPR was associated with a median OS of 40.7 versus 17 months for hemPR and 7.4 months for those without hematologic response (p = 0.028). Cardiac response at 3 months was associated with longer median OS (59.7 vs. 10.9 months, p = 0.044). Factors associated with poorer survival were κ-light chain amyloidosis (median OS 2.9 vs. 7.4 months, p = 0.028), peripheral nerve involvement (3.4 vs. 10.45 months, p = 0.024), systolic blood pressure <90 mmHg (2 vs. 8 months, p = 0.002), baseline LVEF <55% (median OS 3.4 vs. 32 months, p = 0.29) and New York Heart Association (NYHA) class (2.7 months for NYHA 3B-4 vs. 8 months for NYHA 2-3A, p = 0.02). Twenty-one patients (26.3%) received salvage therapy and ORR was 57.1%. Median OS for patients who received second line therapy was 24 months. In conclusion, patients with Mayo 3b disease benefit from early hematologic response but cardiac response rates remain low.
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