Riddhi Patel, Yash Patel, Harshitha Tallapally, Chetan Shah
The co-occurrence of multiple myeloma (MM), systemic immunoglobulin light chain (AL) and heavy-and-light-chain (AHL) amyloidosis, and systemic lupus erythematosus (SLE) presents a highly complex therapeutic challenge. While B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have reshaped the treatment of MM, their safety and efficacy in patients with underlying autoimmune diatheses and severe organ-damaging amyloidosis remain sparsely documented. We report the case of a 67-year-old African American male with a history of SLE who presented with declining renal function and nephrotic-range proteinuria. A renal biopsy in month one revealed AL amyloidosis (Lambda type) with heavy chain (IgG1) co-deposition suggestive of AHL amyloidosis. A subsequent bone marrow biopsy confirmed concurrent MM. The patient was treated with induction chemotherapy (carfilzomib, daratumumab, lenalidomide), followed by an autologous stem cell transplant (ASCT) in month eight. He subsequently received ciltacabtagene autoleucel (cilta-cel) in month 14. By month 16, a bone marrow biopsy confirmed complete marrow remission. At his month 22 follow-up, the patient remained off all antineoplastic agents, demonstrating substantial organ response with near-complete resolution of proteinuria (9.4 mg/dL) and stabilized chronic kidney disease (CKD) stage 3b. Persistent, mild cytopenias and an elevated B-type natriuretic peptide (BNP) prompted ongoing post-CAR-T supportive care and evaluation for cardiac amyloidosis. This case highlights the feasibility of combining ASCT with BCMA-directed CAR T-cell therapy and its association with continued hematologic and renal improvement in highly complex patients with overlapping plasma cell dyscrasias, amyloid deposition, and autoimmune disease.