Identifying Patients with Systemic AL Amyloidosis at the Highest Risk

Systemic AL amyloidosis is a rare blood disorder. It happens when plasma cells make antibodies that are not shaped the way they should be. Instead of Y-shaped antibodies with heavy and light protein chains, the antibodies have too many light protein chains.  This causes misshapen and misfolded antibodies that form amyloid fibrils. These are also called amyloid deposits. 

Amyloid fibrils build up in organs over time. When this happens, your organs do not work the way they should.  Amyloid deposits are commonly seen in the heart, kidneys, liver, and other organs. Outcomes depend on how severely these organs are affected and how well treatment works.

Recent research has suggested adding a high-risk Mayo stage IIIc to the AL amyloidosis staging system for people whose hearts are especially damaged by amyloid deposits. At the 2025 European Hematology Association (EHA) conference, researchers presented data looking at how this group responds to new treatments in comparison to other stage groups. This will help researchers understand if this new stage is still beneficial after treatment advances with daratumumab.   

A new stage group: high-risk Mayo stage IIIc

This new staging system to predict survival in AL amyloidosis is based on blood biomarkers that measure heart stress and injury. In an earlier study, the researchers proposed adding a new category, Mayo Stage IIIc, to the modified Mayo system staging system for AL amyloidosis. This category was designed for patients with severe heart involvement, measured by:

• NT-proBNP greater than 8,500 ng/L, which is a marker of heart strain.

• High-sensitivity troponin T above 50 ng/L, which is a marker of heart injury.

• Myocardial global longitudinal strain (GLS) worse than -9%, which is a heart ultrasound measurement that reflects reduced heart pumping function.

This combination of test results identifies a very small but high-risk group of patients.

How well does daratumumab treat the most high-risk patients? 

Over the past few years, treatment advances first-line therapies combining daratumumab with bortezomib and other medications have improved treatment responses and overall survival for people with AL amyloidosis. Researchers wanted to find out whether this stage IIIc category still identified high-risk patients now that daratumumab-based treatments are widely used.

The study reviewed records from 325 newly diagnosed AL amyloidosis patients between 2015 and 2024. The patients were from the United Kingdom, Greece, and the Netherlands. There were 263 patients (81%) with heart involvement, 189 (58%) with kidney involvement, and 59 (19%) with liver involvement . About 61% received a daratumumab-based treatment, while 29% were treated with a bortezomib combination without daratumumab.

When patients were grouped using the modified Mayo system with the added Stage IIIc category, they found  32 (10%) matched stage IIIc.  

At a median follow-up of 29 months, the two-year overall survival (OS) for all patients was 78%. However, those with stage IIIc AL amyloidosis had a median survival of just 9 months. The stage IIIc category was also highly effective in identifying patients with a poor one-year survival.

Conclusion

Even in the era of daratumumab treatment, the Stage IIIc group remains at very high risk for early death. By adding GLS to the European modified Mayo staging system, doctors can better identify patients who may need additional supportive care, close monitoring, or consideration for innovative treatment strategies.

The researchers plan to validate these findings in a larger patient group. However, this study showed that classifications help identify high-risk patients and design the best treatment strategy. 

Keep reading more updates on the HealthTree News site. 

READ MORE NEWS

Learn more about amyloidosis with HealthTree University. By creating an account, you can track your progress, test your learning, and save your favorite lessons. 

WATCH AMYLOIDOSIS UNIT

Source: 

IDENTIFYING AN ULTRA-POOR RISK ' MAYO STAGE IIIC' GROUP IN SYSTEMIC AL AMYLOIDOSIS IN THE DARATUMUMAB-ERA: A EUROPEAN COLLABORATION