Learn about the latest developments in AL amyloidosis treatment through a comprehensive medical lecture from Dr. Giada Bianchi at Dana-Farber Cancer Institute. Explore fundamental concepts of amyloidoses, focusing on AL amyloidosis as a plasma cell disorder and its pathogenesis related to immunoglobulin free light chain deposition. Gain insights into diagnostic approaches, including cardiac and renal biopsies, and understand why cardiac involvement is the most crucial prognostic factor. Discover the evolution of treatment options, including the groundbreaking Andromeda Study comparing DaraCyBorD versus CyBorD in newly diagnosed patients. Examine the significance of cardiac response criteria, pan-amyloid antibody detection methods, and emerging therapeutic strategies such as Venetoclax-based treatments for t(11;14) cases. Delve into cutting-edge developments in BCMA-targeted therapies, including bispecific T-cell engagers and CAR-T cell treatments, as well as novel approaches using monoclonal antibodies like CAEL-101 for targeting misfolded free light chains.
Overview
Syllabus
Intro
Amyloidoses-Basic Concepts
AL Amyloidosis is a Plasma Cell Disorder
AL Amyloidosis Pathogenesis is Entirely Related to Immunoglobulin Free Light Chain (FLC) Deposition
Pathophysiology
"Stickiness" Dictates Rapidity of Overt Clinical Presentation
AL Amyloidosis Diagnosis
Cardiac Biopsy -H&E
Cardiac Biopsy - Congo Red
Renal Biopsy -Immunofluorescence
Renal Biopsy-Electron Microscopy
Cardiac Involvement is the Single Most Important Prognostic Factor in AL Amyloidosis
Progressive Improvement in OS in AL Amyloidosis
Diagnostic and Therapeutic Considerations
Heme Response Criteria in AL Amyloidosis: the Impact of Deep FLC Suppression
Therapeutic Approach to Newly Diagnosed AL Amyloidosis Patients
The Andromeda Study: DaraCyBorD versus CyBorD in Newly Diagnosed AL Amyloidosis
Andromeda: Patient Characteristics
Superior Hematologic and Organ Response for DaraCyBorD..
Cardiac Response Impact OS in AL Amyloidosis
Graded Cardiac Response Criteria -2022
Complete Cardiac Response Can Potentially Reverse Dismal Outcome of Stage IIIB Patients
Lack of cardiac response and less than VGPR increase risk of cardiac progression
Pan Amyloid Antibody AT-01 to Detect Amyloid Deposition Across the Entire Body
Florbetapir for Early Cardiac Amyloidosis Diagnosis
T(11;14) is the Most Common Cytogenetic Abnormality in AL Amyloidosis, an Adverse Prognostic Factor and a Negative Predict Factor of Response to Bortezomib
T(11;14) is a Predictive Biomarker of Response to Venetoclax in MM
Venetoclax-based Treatment in AL Amyloidosis Appears Effective in t(11;14)
BCMA is a Highly Expressed Protein on the Surface of Plasma Cells and an Ideal Target for Immune- and Cellular Therapies
BCMA Bispecific T-cell Engagers (BITEs)
Teclisimab - the First BITE Approved for Multiple Myeloma
BCMA CAR-T Cell in AL Amyloidosis
CAEL-101, a MoAb Specific to Misfolded FLC, Elicits Cardiac Response in AL Amyloidosis
Pan Amyloid-Targeting Strategies in the Pipeline
The rationale behind combining anti-fibrillary MoAbs and Chemotherapy
Our Pledge at the BWH/DFCI Amyloid Program
Taught by
Dana-Farber Cancer Institute
