Study reveals factors for advanced stage AL amyloidosis outcomes

WASHINGTON: According to new research published in Blood Advances, early improvements in cardiac and hematologic parameters may predict better survival outcomes for patients being treated for stage IIIb AL amyloidosis, a deadly disease with a median survival of 4-6 months caused by abnormal protein buildup.

Amyloidosis develops when normal proteins in the body misfold and form amyloid deposits in vital organs and tissues, resulting in organ dysfunction, failure, and death.

Patients with advanced cardiac amyloidosis have a poor prognosis, but clinicians have little data to guide treatment regimens. The findings of this study show how early responses to treatment can predict survival outcomes.

“While AL amyloidosis is a rare condition, symptoms can mimic those of many other more common diseases, like diabetes, hypertension, autoimmune disorders, and connective tissue diseases, making it difficult for clinicians to diagnose it early,” explained Vaishali Sanchorawala, MD, Director of the Amyloidosis Center at Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, and senior author of this study.

“By understanding the significance of early treatment responses at one and three months after beginning treatment, we can better guide our approaches to therapy and improve patient outcomes.” From 2007 to 2022, researchers examined data from 142 patients with newly diagnosed stage IIIb AL amyloidosis with advanced cardiac involvement. Patients were enrolled after 2007 when bortezomib-based treatment regimens were approved for the treatment of AL amyloidosis following their success in treating myeloma.

Patients had a median overall survival of nine months after 60 months of follow-up. Several baseline factors were predictive of poorer survival, including a longer time from onset of symptoms to diagnosis, a higher bone marrow plasma cell count, higher troponin I levels (a marker of heart damage), and walking less than 200 metres in six minutes. Survival was improved with bortezomib and daratumumab-based regimens.

Patients who had an early hematologic (within one month) and cardiac response had significantly longer overall survival outcomes. Patients who had a very good partial hematologic response one month after treatment had a 47-month survival.

“Stage IIIb AL amyloidosis with advanced cardiac involvement does not have to be a death sentence,” emphasized Dr Sanchorawala.

“We see patients who live four to five years after being diagnosed, and studies like this one helps us understand what factors may indicate a better prognosis. These findings help us to appropriately tailor our treatment regimens to achieve optimal outcomes.” Dr Sanchorawala reiterated that in order to advance treatment and improve overall survival for patients living with this condition, their participation in clinical research must be prioritised.

“Our ability to advance science and improve patient outcomes depends on rare disease-focused clinical trials,” she said.