-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3407 Insights into Presentation and Outcomes of Localized Immunoglobulin Light Chain Amyloidosis: A 12-Year Experience of a Large Academic CenterClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, real-world evidence, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Danai Dima, MD1, Fauzia Ullah, MD1*, Serhan Unlu, MD1*, Diana Basali, MD1, Mahir Khan, MD1*, Abdullah Saeed Khan, MBBS1*, Xuefei Jia, MS2*, Majid Jaberi-Douraki3*, Beth M. Faiman, PhD, CNP1, Sandra Mazzoni, DO1*, Louis S. Williams, MD1, Christy J. Samaras, DO1, Jason Valent, MD1, Faiz Anwer, MD1, Jack Khouri, MD1 and Shahzad Raza, MD1*

1Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
2Department of Biostatistics and Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH
3Department of Mathematics, Kansas State University, DATA Consortium, Computational Comparative Medicine, Olathe, KS

Introduction: Localized immunoglobulin light chain amyloidosis (Loc-AL) is an ultra-rare disease caused by the local deposition of misfolded AL fibrils. To date, limited data exists on reporting patterns of disease presentation and long-term outcomes. The primary aim of this study is to describe our institution’s experience of patients with Loc-AL, including disease presentation, management, and risk for local and systemic progression.

Methods: We retrospectively analyzed medical records of 3108 patients with amyloidosis and selected 141 (5%) patients with biopsy proven Loc-AL treated at our institution between 1/1/2010 and 7/1/2023. Patients with evidence of systemic AL disease involving the bone marrow and/or major organs, such as heart, kidney, liver, and nervous system on initial assessment were excluded. AL amyloid typing was available in all cases; mass spectrometry was performed in 85 (60%) cases. Chi-squared test and Kaplan-Meier method were used for statistical analysis.

Results: Of the 141 patients with Loc-AL included in this analysis, 79 (56%) were female and 117 (83%) were White. The median age at diagnosis was 67 (range 18-92) years. The sites of involvement included: 22% lower respiratory system (16% lung/pleura, 4% tracheobronchial system, 2% multi-site), 18% gastrointestinal system (8% upper GI [esophagus, stomach, duodenum] tract, 9% lower GI [colon, rectum] tract, and 1% other), 18% head & neck (eye [conjunctiva, lacrimal sac], auditory canal, oral cavity, pharynx/oropharynx), 9% urothelial system (prostate, bladder, ureteral, urethra), 9% soft tissue, 7% skin, 7% breast, 4% upper respiratory system (vocal cords, larynx, subglottic area), and 6% others (including two cases of central nervous system involvement) (Figure 1). At presentation, 75 (53%) patients were symptomatic, whereas in the remaining 65 (47%) patients Loc-AL was an incidental finding. Bone marrow biopsy, fat pad biopsy and cardiac imaging (echocardiogram and/or cardiac MRI) were obtained in 67 (48%), 20 (14%) and 105 (74%) patients, respectively. All bone marrow and pad biopsies were negative for AL amyloid; in addition, no bone marrow biopsy revealed monoclonal plasma cells. A serum monoclonal protein (sMP) was detected in only 29 (20%) patients, 12 of whom had serum light chain different from the localized light chain type. Of the 29 patients with positive sMP, 20 had IgG isotype, 6 had IgM, 2 IgA and 1 had light chains only. Abnormal free light chain ratio was reported in 17 (12%) patients, 6 of whom had a positive sMP. Twenty-four (17%) patients had coexistent autoimmune disease and 13 (9%) co-existent malignancy that was not plasma cell related. First line management approaches included: observation with or without supportive care (57%), surgical resection (38%), radiotherapy (2%), systemic therapy (3.5% chemotherapy, 3.5% steroids) and topical therapy (3.5%). Of the 5 patients who received chemotherapy, 4 had plasma cell-directed therapy; of them, 3 maintained stable disease based on follow-up imaging and 1 had no response. The fifth patient received rituximab for their underlying MALT lymphoma. Seventeen patients (12%) required repeated interventions (median 1 [range 1-4]) for local disease progression. The most common sites requiring repeated interventions were: genitourinary system (29%), respiratory system (24%) and breast (18%). No patient progressed to systemic AL. There were no deaths attributed to Loc-AL. The median follow-up time was 46.7 months. The 2- and 5-year local progression free survival rates were 93%, and 78%, respectively, and there was no difference with regard to site of disease. The estimated median overall survival (OS) was not reached; the 2- and 5-year OS rates were 99% and 92%, respectively (Figure 2).

Conclusion: The results of our study suggest that Loc-AL has an excellent prognosis, and does not progress to systemic AL disease. A significant number of patients have no symptoms at diagnosis. Observation and/or surgical removal are usually adequate initial approaches to manage Loc-AL, however, a small percentage of patients can relapse locally requiring repeated interventions for symptom control. Consultation with a hematologist is important to rule out systemic disease.

Disclosures: Williams: Bristol Meyers Squibb: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Valent: Alexion, AstraZeneca Rare Disease: Research Funding. Khouri: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; GPCR Therapeutics: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. Raza: Prothena: Honoraria; Pfizer: Honoraria; Kite Pharma: Honoraria; Autolus Therapeutics: Current holder of stock options in a privately-held company; ATARA Therapeutics: Current holder of stock options in a privately-held company.

*signifies non-member of ASH