**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.**
Jahanzaib Khwaja, University College London Hospitals, London

**Main Body of the Abstract**
Introduction: 
The addition of daratumumab to bortezomib-cyclophosphamide-dexamethasone (VCD) significantly improved outcomes for treatment-naïve AL in ANDROMEDA. An immunomodulatory agent-based quadruplet has not been investigated as first-line treatment in AL. We report the UK experience of daratumumab-bortezomib-thalidomide-dexamethasone (DVTD) in patients with treatment-naïve AL amyloidosis.

Methods: 
Treatment-naïve patients with systemic AL between 2021-2023 proceeding with DVTD were retrospectively reviewed from the UK National Amyloidosis Centre. Daratumumab was administered for 4 cycles (weekly subcutaneous 1800mg, cycles 1-2; biweekly cycles 3-4) with 6 cycles subcutaneous bortezomib (1-1.3mg/m2 weekly) and thalidomide (D1-28 50mg, omitted in cycle 1). Individual clinicians modified doses as per patient tolerance.

Results: 
Ninety-nine patients (62M, 37F) commenced DVTD. Baseline characteristics are outline (table 1). Median follow-up was 10 (0-26) months; a median of 6 (0-8) cycles were delivered. By intention-to-treat analysis, best haematological responses were CR:61%, VGPR:20%, PR:15%, NR:4% at a median of 6 (1-66) weeks in responders. Nine patients died (Mayo IIIb: 3; IIIa: 4; II: 2); 2/9 due to unrelated malignancy whilst in VGPR/CR. Six proceeded with HDM-ASCT consolidation after DVTD induction. Overall, 6 patients (CR:1, VGPR:3, PR:2) progressed, requiring second-line IMiD-based therapy. Median OS was not reached for any Mayo subgroup. Estimated 1-year OS was 89% (95% CI 78-94) and for Mayo I, II, IIIa, IIIb was 100%, 93%, 79%, 82%. Estimated 1-yr treatment-free-survival/death was 79% (95% CI 67-88).

Conclusion: 
This series supports the use of dose-modified DVTD in first-line AL amyloidosis including in those with Mayo IIIb/renal impairment, with rapid and deep responses achievable, comparable with DVCD.



**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.**
Jahanzaib Khwaja, University College London Hospitals, London

**Main Body of the Abstract**
**Introduction:** 
The addition of daratumumab to bortezomib-cyclophosphamide-dexamethasone (VCD) significantly improved outcomes for treatment-naïve AL in ANDROMEDA. An immunomodulatory agent-based quadruplet has not been investigated as first-line treatment in AL. We report the UK experience of daratumumab-bortezomib-thalidomide-dexamethasone (DVTD) in patients with treatment-naïve AL amyloidosis.

**Methods:** 
Treatment-naïve patients with systemic AL between 2021-2023 proceeding with DVTD were retrospectively reviewed from the UK National Amyloidosis Centre. Daratumumab was administered for 4 cycles (weekly subcutaneous 1800mg, cycles 1-2; biweekly cycles 3-4) with 6 cycles subcutaneous bortezomib (1-1.3mg/m^2^ weekly) and thalidomide (D1-28 50mg, omitted in cycle 1). Individual clinicians modified doses as per patient tolerance.

**Results:** 
Ninety-nine patients (62M, 37F) commenced DVTD. Baseline characteristics are outline (table 1). Median follow-up was 10 (0-26) months; a median of 6 (0-8) cycles were delivered. By intention-to-treat analysis, best haematological responses were CR:61%, VGPR:20%, PR:15%, NR:4% at a median of 6 (1-66) weeks in responders. Nine patients died (Mayo IIIb: 3; IIIa: 4; II: 2); 2/9 due to unrelated malignancy whilst in VGPR/CR. Six proceeded with HDM-ASCT consolidation after DVTD induction. Overall, 6 patients (CR:1, VGPR:3, PR:2) progressed, requiring second-line IMiD-based therapy. Median OS was not reached for any Mayo subgroup. Estimated 1-year OS was 89% (95% CI 78-94) and for Mayo I, II, IIIa, IIIb was 100%, 93%, 79%, 82%. Estimated 1-yr treatment-free-survival/death was 79% (95% CI 67-88).

**Conclusion:** 
This series supports the use of dose-modified DVTD in first-line AL amyloidosis including in those with Mayo IIIb/renal impairment, with rapid and deep responses achievable, comparable with DVCD.



Outcomes of Daratumumab Bortezomib Thalidomide Dexamethasone in treatment-naïve systemic AL amyloidosis  PA155 (#238)

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.