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ASH 2025 | Durability of MRD in AL amyloidosis: the impact on clinical outcomes
Andrew Staron, MD, Boston Medical Center, Boston, MA, discusses how the durability of measurable residual disease (MRD) affects clinical outcomes in light chain amyloidosis. He highlights that sustained MRD negativity is a strong predictor of long-term disease control and notes that serial MRD monitoring can identify patients who are at risk of clinical relapse and progression. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
Our study investigates how durability of MRD affects clinical outcomes in patients with AL amyloidosis who already have achieved hematologic complete response by traditional consensus criteria. Even when patients achieve hematologic complete response, small amounts of clonal plasma cells can remain in the bone marrow, and this can lead to future clinical relapse and progression. Using highly sensitive multiparametric flow cytometry, we at the Boston University Amyloidosis Center have been tracking MRD status in real-world clinical settings since 2019...
Our study investigates how durability of MRD affects clinical outcomes in patients with AL amyloidosis who already have achieved hematologic complete response by traditional consensus criteria. Even when patients achieve hematologic complete response, small amounts of clonal plasma cells can remain in the bone marrow, and this can lead to future clinical relapse and progression. Using highly sensitive multiparametric flow cytometry, we at the Boston University Amyloidosis Center have been tracking MRD status in real-world clinical settings since 2019. What we really wanted to better understand is whether sustained MRD negativity, meaning having negative MRD results over time, better predicts prognosis as opposed to just a single MRD measurement. We analyzed 106 patients using serial MRD monitoring. Overall, we found that 40% of patients achieved sustained MRD negativity. And this seemed to be true across different treatment histories, including patients who were newly diagnosed after the first line of treatment, as well as relapse patients who had received two or more lines of therapy. We also saw this across different treatment types, including stem cell transplantation and daratumumab-based treatments. When looking at clinical outcomes, the results were striking. None of the patients who had sustained MRD negativity went on to experience hematologic progression. In contrast, nearly half of patients who had MRD positivity went on to have either hematologic or organ progression. Furthermore, we observed that some patients who were initially MRD negative experienced MRD resurgence, meaning they later went on to test MRD positive. And many of these individuals later had clinical progression, often occurring one to two years after MRD resurgence. So our study findings show that MRD is dynamic in AL amyloidosis and that a single MRD check is probably not enough. Sustained MRD negativity is a strong marker of long-term disease control, and MRD resurgence may serve as an early warning signal. So in short, MRD, serial longitudinal MRD monitoring adds value to post-treatment surveillance in AL amyloidosis, helping us to identify which patients truly have sustained disease control and which patients need closer follow-up monitoring.
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