Diagnostic Test Accuracy of Fat Pad Sampling and Bone Marrow Biopsies in the Diagnosis of AL Amyloidosis: A Systematic Review and Meta-Analysis

Introduction:

Tissue biopsies are needed to establish a diagnosis of systemic AL amyloidosis. Biopsy can be obtained from an involved organ with suspected amyloid deposition (target biopsy) or from sites in which amyloid commonly deposits (surrogate biopsy). The choice of biopsy site depends on institutional and physician preference. Two commonly used sites for surrogate biopsies are abdominal fat pad and bone marrow. The present systematic review and meta-analysis aims to evaluate the diagnostic test accuracy of fat pad and bone marrow biopsies as surrogate biopsy sites in the diagnosis of AL amyloidosis.

Methods:

As part of the ASH AL Amyloidosis Diagnostic Guideline, we performed systematic reviews for seven prioritized PICO questions related to the screening, diagnosis and organ involvement evaluation of AL amyloidosis. We conducted electronic searches on PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception until January 2024. Two reviewers independently and in duplicate performed title and abstract screening and full text article screening on LASER AI, with conflicts resolved by a third reviewer.

Studies were eligible if they included patients that had a fat pad sample or bone marrow biopsy and a target organ biopsy for suspicion of AL amyloidosis allowing for the calculation of diagnostic test accuracy measures. Diagnostic test accuracy measures of interest were sensitivity, specificity, positive and negative predictive value. Statistical analysis was performed on OpenMeta[Analyst]. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence.

Results:

After deduplication, we retrieved 29,237 studies.. 20 studies with 2955 patients reporting on bone marrow biopsy, 25 with 4702 patients on fat pad sampling were included. The pooled sensitivity for bone marrow biopsy was 55.1% (95% CI 45.8-64.0, I² = 94%) (Certainty of evidence: Low ⨁⨁◯◯), For fat pad sampling sensitivity was 76.6% (95% CI 72.1-80.8, I2 = 84.2%) (Certainty of evidence: Moderate ⨁⨁⨁◯). Among the included studies, 1 evaluated the sensitivity of fat pad sampling and bone marrow biopsy combined and found it to be 89%. No included studies evaluated specificity for bone marrow biopsy or fat pad sample.

Conclusion:

Combination of fat pad and bone marrow biopsy together significantly improve sensitivity for amyloid detection compared to either fat pad sampling or bone marrow biopsy alone.

Seftel:Astrazeneca: Other: Meal at CME event; Novartis: Other: Meal at CME event. Carroll:Janssen: Other: Travel Support; Alnylam: Other: Advisory Committee; CSL Behring: Honoraria. Dispenzieri:Alnylam: Research Funding; Alexion: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Research Funding; HaemaloiX: Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Research Funding. Khouri:Prothena: Honoraria; Legend: Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics, Inc.: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant. Raza:Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Aguirre:Pfizer: Honoraria; PTC Bio: Honoraria. Bumma:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cook:Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Jamal:Janssen: Consultancy. Dasgupta:Intellia: Other: Advisory Board; Astra Zeneca: Other: Advisory Board; Alnylam: Other: Advisory Board; NovoNordisk: Other: Advisory Board; Eidos: Other: Advisory Board; Siemens: Other: Adjudicator. Leung:Checkpoint Therapeutics: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company. Sanchorawala:Proclara, Caelum, Abbvie, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena, AstraZeneca, Nexcella: Membership on an entity's Board of Directors or advisory committees; Pfizer, Janssen, Attralus, GateBio, Abbvie, BridgeBio: Consultancy; Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, Caelum, Alexion: Research Funding. Sarswat:Eidos: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees.