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.
Rajshekhar Chakraborty, Columbia University Irving Medical Center, New York, NY

Main Body of the Abstract
Background: The prognostic significance of cytogenetic abnormalities by FISH in the context of daratumumab-based frontline therapy is not well-defined.
Methods: We conducted a multicenter retrospective cohort study investigating Dara-VCD/Dara-VD efficacy in cytogenetic subgroups: t(11;14), +1q, hyperdiploidy, deletion(13q), and high-risk abnormalities (t(4;14), t(14;16), t(14;20), and/or del(17p)). Key endpoints included heme-CR rate, ≥heme-VGPR rate, and hematologic event-free survival (Heme-EFS: time from treatment initiation to subsequent therapy/death)
Results: A total of 267 patients who had started Dara-VCD/Dara-VD by 12/31/2022 were included, with 244 having baseline FISH. The incidence of abnormalities was as following: t(11;14)-52%; deletion(13q)-30%; hyperdiploidy-29%; +1q-22%; and HR-9%. The heme-CR rate by cytogenetic subgroups was as follows: t(11;14) vs no t(11;14)-50.0% vs 44.3% (p=0.419); +1q vs no +1q-33.3% vs 52.1% (p=0.026); hyperdiploidy vs no hyperdiploidy-41.7% vs 49.3% (p=0.409); del(13q) vs no del(13q)-48.3% vs 48.1% (p=0.978); and HR vs no HR: 56.3% vs 46.3% (p=0.445). Similarly, +1q was the only subgroup with a significantly lower ≥heme-VGPR rate (66.7% vs 83.1%; p=0.023). At a median follow-up of 20.0 months, the median heme-EFS was 49.6 months (95% CI, 24.7-NR), and 2-year OS was 81.5% (95% CI, 75.8-86.1). Among cytogenetic subgroups, +1q was the only subgroup with a significantly worse heme-EFS compared to no +1q (median, 15.2 months vs NR, respectively; p=0.044; Figure I).
Conclusion: In the Dara-VCD/Dara-VD frontline therapy era, +1q presence is linked to lower deep hematologic response rates and poorer heme-EFS compared to its absence. On the other hand, t(11;14) is no longer linked to worse outcomes in the daratumumab-era.

**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.**
Rajshekhar Chakraborty, Columbia University Irving Medical Center, New York, NY

**Main Body of the Abstract**
**Background**: The prognostic significance of cytogenetic abnormalities by FISH in the context of daratumumab-based frontline therapy is not well-defined.
**Methods**: We conducted a multicenter retrospective cohort study investigating Dara-VCD/Dara-VD efficacy in cytogenetic subgroups: t(11;14), +1q, hyperdiploidy, deletion(13q), and high-risk abnormalities (t(4;14), t(14;16), t(14;20), and/or del(17p)). Key endpoints included heme-CR rate, ≥heme-VGPR rate, and hematologic event-free survival (Heme-EFS: time from treatment initiation to subsequent therapy/death)
**Results**: A total of 267 patients who had started Dara-VCD/Dara-VD by 12/31/2022 were included, with 244 having baseline FISH. The incidence of abnormalities was as following: t(11;14)-52%; deletion(13q)-30%; hyperdiploidy-29%; +1q-22%; and HR-9%. The heme-CR rate by cytogenetic subgroups was as follows: t(11;14) vs no t(11;14)-50.0% vs 44.3% (p=0.419); +1q vs no +1q-33.3% vs 52.1% (p=0.026); hyperdiploidy vs no hyperdiploidy-41.7% vs 49.3% (p=0.409); del(13q) vs no del(13q)-48.3% vs 48.1% (p=0.978); and HR vs no HR: 56.3% vs 46.3% (p=0.445). Similarly, +1q was the only subgroup with a significantly lower ≥heme-VGPR rate (66.7% vs 83.1%; p=0.023). At a median follow-up of 20.0 months, the median heme-EFS was 49.6 months (95% CI, 24.7-NR), and 2-year OS was 81.5% (95% CI, 75.8-86.1). Among cytogenetic subgroups, +1q was the only subgroup with a significantly worse heme-EFS compared to no +1q (median, 15.2 months vs NR, respectively; p=0.044; Figure I).
**Conclusion**: In the Dara-VCD/Dara-VD frontline therapy era, +1q presence is linked to lower deep hematologic response rates and poorer heme-EFS compared to its absence. On the other hand, t(11;14) is no longer linked to worse outcomes in the daratumumab-era.

Prognostic impact of cytogenetic abnormalities by FISH in systemic AL amyloidosis in the era of daratumumab and bortezomib-based frontline combination regimens PA106 (#35)

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.