P-008: First report of a patient with systemic light chain amyloidosis in the course of Multiple Myeloma treated with CAR T cells directed against B-cell maturation antigen

Abstract

<h3>Background</h3> 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 a light-chain (AL) amyloidosis due to the deposition of amyloidogenic light chains causing organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become the most promising approach in treating cancer patients, especially hematologic 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. <h3>Methods</h3> A 61-year-old woman diagnosed with an IgA-lambda symptomatic MM in 2014, with several prior lines of treatment presented with edema and significant non-selective albuminuria (24-hour proteinuria of 2626 mg with urinary M-protein of 307 mg, serum albumin 28 g/L) with preserved renal function (creatinine 0.6 mg/dL) and an increase in serum M protein, with a bone marrow (BM) infiltration by 23% plasma cells. There was no evidence of extramedullary disease by PET-CT and no CRAB signs were found. A subcutaneous fat aspiration and a renal biopsy established the diagnosis of systemic AL amyloidosis without cardiac involvement. At this point AL amyloidosis was the main reason to treat the patient, who received a fractioned dose of 3×10⁶/kg BCMA-CAR T cells after lymphodepletion, developing a grade I cytokine release syndrome and treatment-related cytopenias (grade 4 neutropenia and grade 2 thrombocytopenia), with no neurotoxicity. <h3>Results</h3> On day +28, the patient had already obtained a deep hematologic response with negative measurable residual disease by flow cytometry in the BM. After 3 months, the patient maintained the hematologic complete response and achieved renal response. After 1 year follow-up, the patient remains in hematologic complete remission and renal response with a decrease in proteinuria of 70%. <h3>Conclusions</h3> Here, we present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of a MM, successfully treated with CART therapy targeting BCMA. 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.