**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Ioannis V. Kostopoulos
Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece

**Main Body of the Abstract**
Background: There is a constant need for the identification of novel biomarkers that could efficiently improve risk stratification in AL amyloidosis. In this study we evaluated the prognostic impact of circulating tumor cells (CTCs) in previously untreated patients with AL amyloidosis, which has correlated with adverse clinical outcomes in multiple myeloma.  Methods: The presence of CTCs was assessed with next generation flow cytometry (NGF) in 179 consecutive patients at diagnosis, according to Euroflow guidelines. The same approach was used for the assessment of minimal residual disease (MRD) in patients achieving hemVGPR/hemCR ≥6 months post treatment initiation. The median follow-up was 24 months (range: 6-72 months).
Results: With a median limit of detection reaching 2.2x10-6, CTCs were detected in 106/179 (59%) patients with a median value of 0.0015% of total nucleated cells. The absence of CTCs correlated with lower LDH levels(p=0.001), NTproBNP(p=0.007), dFLC(p=0.01) and BM infiltration(p<0.001); there was no correlation with organ involvement patterns. Regression analysis did not show correlation between baseline CTCs and probability or time to CR achievement. However, patients with detectable CTCs had a 4.2-fold higher risk of not reaching MRD negativity (p<0.0001). Patients with CTC levels ≥10-3 (n=15, 8.4%) had poorer outcomes with a median OS of only 15 months (HR: 2.4, 95% CI:1.2-5.1, p<0.01).
Conclusion: NGF allows for the detection of CTCs in the majority of patients with AL amyloidosis, the presence of which is associated with adverse prognostic features and a lower probability of achieving deep hematologic responses.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Ioannis V. Kostopoulos
Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece

**Main Body of the Abstract**
**Background:** There is a constant need for the identification of novel biomarkers that could efficiently improve risk stratification in AL amyloidosis. In this study we evaluated the prognostic impact of circulating tumor cells (CTCs) in previously untreated patients with AL amyloidosis, which has correlated with adverse clinical outcomes in multiple myeloma.  **Methods:** The presence of CTCs was assessed with next generation flow cytometry (NGF) in 179 consecutive patients at diagnosis, according to Euroflow guidelines. The same approach was used for the assessment of minimal residual disease (MRD) in patients achieving hemVGPR/hemCR ≥6 months post treatment initiation. The median follow-up was 24 months (range: 6-72 months).
**Results:** With a median limit of detection reaching 2.2x10-6, CTCs were detected in 106/179 (59%) patients with a median value of 0.0015% of total nucleated cells. The absence of CTCs correlated with lower LDH levels(p=0.001), NTproBNP(p=0.007), dFLC(p=0.01) and BM infiltration(p<0.001); there was no correlation with organ involvement patterns. Regression analysis did not show correlation between baseline CTCs and probability or time to CR achievement. However, patients with detectable CTCs had a 4.2-fold higher risk of not reaching MRD negativity (p<0.0001). Patients with CTC levels ≥10-3 (n=15, 8.4%) had poorer outcomes with a median OS of only 15 months (HR: 2.4, 95% CI:1.2-5.1, p<0.01).
**Conclusion:** NGF allows for the detection of CTCs in the majority of patients with AL amyloidosis, the presence of which is associated with adverse prognostic features and a lower probability of achieving deep hematologic responses.



Prognostic significance of circulating tumor cells assessed with next generation flow cytometry in patients with AL amyloidosis PA136 (#550)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.