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4671 Clinical Characteristics and Treatment Outcomes of Patients with AL Amyloidosis with Acquired Factor X Deficiency

Program: Oral and Poster Abstracts
Session: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Epidemiology, Clinical Research, Health outcomes research
Monday, December 9, 2024, 6:00 PM-8:00 PM

Okan Cetin, MD1*, Patric Teodorescu, MD2*, Andrew Staron, MD3, Vaishali Sanchorawala3 and Raphael E. Szalat, MD, PhD4

1Department of Medicine, Istanbul University School of Medicine, Istanbul, AL, Turkey
2Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
3Amyloidosis Center, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
4Section of Hematology and Medical Oncology, Boston Medical Center, Boston, MA

Background:

Acquired factor X (aFX) deficiency is a rare but significant complication associated with AL Amyloidosis, potentially resulting from FX adsorption by amyloid fibrils. aFX increases the risk of hemorrhagic complications inherent to AL amyloidosis. We aimed to describe the clinical characteristics and outcomes of patients with aFX deficiency and AL amyloidosis evaluated at a tertiary amyloidosis center.

Methods:

We conducted a retrospective study of patients with FX deficiency evaluated at the Boston University Amyloidosis Center from 2000 to 2023, and collected data on demographics, clinical characteristics, treatments, and outcomes. FX deficiency was defined as a FX activity of ≤50% in absence of any anticoagulation therapy. All patients consented to the use of clinical data in research, and the study was approved by the Institutional Review Board in accordance with the Declaration of Helsinki.

Results

Among 1956 patients who had at least one FX measurement during the study period, 256 had ≤ 50% FX activity. Of these, 132 patients were excluded due to concomitant anticoagulation therapy and 36 due to incomplete medication history. Thus, 88 patients with FX deficiency were included in this study. 66 (75%) patients were male with a median age of 59 years (range, 36–85) and 18 (21%) self-identified as a non-white race. The most common clinical manifestations were ecchymoses 35%, periorbital ecchymoses 15%, and gastrointestinal bleeding 15%. The median FX activity was 39.5% (range, 5-50%). Seventy-seven patients had AL amyloidosis alone, 10 patients had multiple myeloma associated with AL amyloidosis, and 1 patient had Waldenstrom’s macroglobulinemia-associated AL amyloidosis. The light-chain isotype was lambda in 70 (80%) patients. Patients were categorized as having mild (41-50%, n=41), moderate (21-40%, n=33), and severe (≤20%, n=15) FX deficiency. 72 patients (82%) had > 2 organ involvement including renal (n=69, 79%), cardiac (n=64, 73%), nervous system(n=46, 52%), and liver (n=30, 34%). Renal and liver involvement were more frequent in patients with moderate and severe FX deficiency.

Longitudinal FX activity levels were available post-initial therapy for thirty patients. First-line treatment regimens included high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT, n=11); cyclophosphamide, bortezomib, and dexamethasone (CyBorD, n=10); daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD, n=4); and others (n=5). Out of eleven patients who underwent the HDM/SCT group, 3 patients had grade 3, and 2 patients had grade 1 bleeding complications within the first month of treatment. Overall, FX activity improved to >50% in 73% (n=22/30) patients, and the median overall survival was 73 months (range, 6-172). Twenty-eight patients were evaluable for hematologic response, with a complete response (hemCR) achieved in 10 (36%) patients at 12 months post-treatment, resulting in a median FX improvement of 42% (range, -15 to 112). In contrast, 18 (64%) patients did not achieve a hemCR and had a median FX improvement of 14% (range, -10 to 64). FX activity increased by a median of 28% at 12 months after HDM/SCT compared to 14% after non-SCT treatment regimens.

Conclusion:

In AL amyloidosis, aFX deficiency is rare and typically associated with multiple organ involvement. FX levels improve with treatment in most patients and correlate with the depth of hematologic response. HDM/SCT is associated with the highest rates of FX improvement but also a higher risk of hemorrhagic complications during treatment. Further studies are needed to clarify the relationship between Factor X improvement and different treatment regimens.

Disclosures: Sanchorawala: Proclara, Caelum, Abbvie, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena, AstraZeneca, Nexcella: Membership on an entity's Board of Directors or advisory committees; Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, Caelum, Alexion: Research Funding; Pfizer, Janssen, Attralus, GateBio, Abbvie, BridgeBio: Consultancy.

*signifies non-member of ASH