**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.**
Brendan Hudson Saunders, Brigham and Women's Hospital, Boston, MA

**Main Body of the Abstract**
Background: A difference between involved and non-involved free light chain (dFLC) exceeding 180 mg/L is part of the 2012 Mayo staging system. We hypothesized that depth of response in AL amyloidosis patients treated with bortezomib-containing regimens are independent of free light chain burden.
Methods: This is a retrospective, multicentre study including 223 newly diagnosed AL amyloidosis patients seen at our institutions between 2012 to 2024. We investigated the relationship between baseline iFLC and dFLC at day 28 and 3, 6, 9 and 12 months from commencement of CyBorD or DaraCyBorD therapy. The study was IRB approved.
Results: We identified 132 patients treated with CyBorD and 91 treated with DaraCyBorD. Forty patients in the CyBorD cohort and 3 in the DaraCyBorD cohort did not respond to therapy. Lack of response was independent of baseline iFLC. At day 28, we identified no correlation (r2=0.02) between baseline iFLC and dFLC response in patients receiving DaraCyBorD (Fig 1A), while patients receiving CyBorD had lower cytoreduction (r2=0.53), particularly when iFLC measured >1000mg/L (Fig 1B). Similar trends were noted at 3, 6, 9 and 12 months from therapy start.
Conclusion: Depth and rapidity of response is independent of iFLC at diagnosis in patients treated with DaraCyBorD.  Response in CyBorD treated patients is weakly dependent on baseline iFLC at exceedingly high values. Data from our cohort are not mature to assess overall survival, but it questions the importance of free light chain burden measured by conventional methods (sFLC) in the era of DaraCyBorD.



**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.**
Brendan Hudson Saunders, Brigham and Women's Hospital, Boston, MA

**Main Body of the Abstract**
**Background:** A difference between involved and non-involved free light chain (dFLC) exceeding 180 mg/L is part of the 2012 Mayo staging system. We hypothesized that depth of response in AL amyloidosis patients treated with bortezomib-containing regimens are independent of free light chain burden.
**Methods:** This is a retrospective, multicentre study including 223 newly diagnosed AL amyloidosis patients seen at our institutions between 2012 to 2024. We investigated the relationship between baseline iFLC and dFLC at day 28 and 3, 6, 9 and 12 months from commencement of CyBorD or DaraCyBorD therapy. The study was IRB approved.
**Results:** We identified 132 patients treated with CyBorD and 91 treated with DaraCyBorD. Forty patients in the CyBorD cohort and 3 in the DaraCyBorD cohort did not respond to therapy. Lack of response was independent of baseline iFLC. At day 28, we identified no correlation (r^2^=0.02) between baseline iFLC and dFLC response in patients receiving DaraCyBorD (Fig 1A), while patients receiving CyBorD had lower cytoreduction (r^2^=0.53), particularly when iFLC measured >1000mg/L (Fig 1B). Similar trends were noted at 3, 6, 9 and 12 months from therapy start.
**Conclusion:** Depth and rapidity of response is independent of iFLC at diagnosis in patients treated with DaraCyBorD.  Response in CyBorD treated patients is weakly dependent on baseline iFLC at exceedingly high values. Data from our cohort are not mature to assess overall survival, but it questions the importance of free light chain burden measured by conventional methods (sFLC) in the era of DaraCyBorD.



Predictive value of free light chain burden in patients newly diagnosed with AL amyloidosis treated with CyBorD or DaraCyBorD PA121 (#348)

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.