First third-generation CAR T cell application targeting CD19 for the treatment of systemic IgM AL amyloidosis with underlying marginal zone lymphoma

• Main Authors: Felix Korell (Author), Stefan Schönland (Author), Anita Schmitt (Author), Madelaine Jansen (Author), Kiavasch Farid (Author), Carsten Müller-Tidow (Author), Peter Dreger (Author), Michael Schmitt (Author), Ute Hegenbart (Author)
• Format: Book
• Published: BMC, 2023-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Abstract Light chain amyloidosis (AL) is a rare disease caused by the generalized deposition of misfolded free light chains. Patients with immunoglobulin M gammopathy (IgM) and indolent B-cell lymphoma such as marginal zone lymphoma (MZL) may in some instances develop AL amyloidosis. So far, CAR T cells for AL amyloidosis have only been reported utilizing the B cell maturation antigen as target, while CD19 has so far not been used in AL amyloidosis. We report the case of a 71-year-old male, diagnosed with systemic AL kappa amyloidosis and MZL, receiving third-generation CAR T cell therapy targeting CD19. Prior treatment included bendamustine/rituximab and cyclophosphamide/ dexamethasone with subsequent autologous stem cell transplantation. CAR T application was well tolerated despite heart and kidney amyloid manifestations, and only early low-grade procedure-specific toxicities were observed. A continuous decrease in IgM, kappa light chains and kappa-to-lambda light chain difference was observed in the patient from day + 30 on, resulting in a deep hematological response six months after treatment. In summary, we present a novel case of CAR T cell treatment with third generation CD19 directed infusion for AL amyloidosis with an underlying secretory active B cell lymphoma, showing that this is an effective treatment modality and can be applied to patients with subsequent AL amyloidosis.

Item Description

10.1186/s40364-023-00532-2
2050-7771