First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma

Abstract

Multiple myeloma (MM) remains incurable despite the number of novel therapies that have become available in recent years. Occasionally, a patient with MM will develop an amyloid light-chain (AL) amyloidosis with organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become a promising approach in treating hematological malignancies. Our institution has developed a second-generation B-cell maturation antigen (BCMA)-CART which is currently being tested in a clinical trial for relapsed/refractory MM.We present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of an MM, successfully treated with CART therapy targeting BCMA. The patient received a fractioned dose of 3×106/kg BCMA-CARTs after lymphodepletion. At 3 months from infusion, the patient had already obtained a deep hematological response with negative measurable residual disease by flow cytometry in the bone marrow. After 12 months, the patient remains in hematological stringent complete remission and has achieved an organ renal response with a decrease of 70% of proteinuria.This case suggests that concomitant AL amyloidosis in the setting of MM can benefit from CART therapy, even in patients in which predominant symptoms at the time of treating are caused by AL amyloidosis.

Trial registration: ClinicalTrials.gov NCT04309981.

Keywords: chimeric antigen; hematological neoplasms; immunotherapy; receptors.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Diagnosis and immunohistochemical typing of amyloidosis. Evolution of clinical and laboratory findings after infusion of ARI0002h. Diagnosis of amyloid deposits in a fine-needle aspiration of subcutaneous fatty tissue: (A) Congo red-stained tissue section, amyloid deposits highlighted with horizontal arrows; (B) Congo red green birefringence, amyloid deposits highlighted with horizontal arrows. Immunohistochemical typing of the renal amyloidosis as ALλ type shown on adjacent sections and amyloid deposits highlighted with horizontal arrows: (C) Congo red-stained (D) anti-ALλ showing positivity on amyloid deposits; (E) anti-ALκ and (F) anti-AA showing negativity on amyloid deposits. Magnification ×100. Amyloid was not evident in the bone marrow section. (G) In the first 6 months after infusion of ARI0002h, a progressive decline in serum M-protein and lambda sFLC was observed. MRD was negative on day +28 and remains negative at 12 months. A renal response with a 55% and 70% decrease in proteinuria was observed at 6 and 12 months, with an intermediate period in which, due to hemorrhagic cystitis, proteinuria is not assessable. Expansion of CARTs by either flow cytometry and qRT-PCR are also represented, with a peak at day +21. AL, amyloid light-chain; CART, chimeric antigen receptor T cell; MRD, minimal residual disease; sFLC, serum free light chain.