Abstract: SA-PO0771
A Novel Case of Paraprotein-Mediated Complement Dysregulation in Refractory Heavy-Chain Deposition Disease
Session Information
- Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Chadha, Ashima, Mass General Brigham Inc, Boston, Massachusetts, United States
- Niles, John L., Mass General Brigham Inc, Boston, Massachusetts, United States
- Laliberte, Karen A., Mass General Brigham Inc, Boston, Massachusetts, United States
- Smith, Rex Neal, Mass General Brigham Inc, Boston, Massachusetts, United States
- Yee, Andrew J., Mass General Brigham Inc, Boston, Massachusetts, United States
- Efe, Orhan, Mass General Brigham Inc, Boston, Massachusetts, United States
- Al Jurdi, Ayman, Mass General Brigham Inc, Boston, Massachusetts, United States
- Seethapathy, Harish Shanthanu, Mass General Brigham Inc, Boston, Massachusetts, United States
Introduction
Heavy Chain Deposition Disease (HCDD) is a rare subtype of monoclonal gammopathy of renal significance characterized by non-organized deposition of truncated immunoglobulin heavy chains, often with concomitant C3 deposition. Reported outcomes in HCDD treated with clone-directed therapy vary, and the role for complement inhibition in its management is undefined. We present a rare case of daratumumab-refractory HCDD complicated by severe complement dysregulation, highlighting key management considerations.
Case Description
A 72-year-old male presented with acute kidney injury and nephrotic syndrome with negative serologic evaluation. Renal biopsy was consistent with IgG1 heavy chain deposition disease (Fig 1). While urine and blood clone detection studies were negative, bone marrow biopsy exposed a monotypic IgG lambda plasma cell population. He began clone-directed therapy with daratumumab with initial improvement but experienced relapsing nephrotic syndrome at 15 months despite ongoing treatment. Renal function declined from serum creatinine 1.7 to 2.9 mg/dL, proteinuria increased from nadir 0.1 to 6.27 g/g, and he developed a new decline in FLCR to 0.2 and hypocomplementemia with C3 75 mg/dL. His disease progressed despite intensification of therapy with bortezomib and dexamethasone. Repeat renal biopsy showed progression of HCDD with increased density of deposits and heavy C3 deposition, concerning for complement dysregulation precipitated by monoclonal disease (Fig 1). He is currently receiving treatment with elranatamab (bispecific B-cell maturation antigen-directed CD3 T-cell engager), with the addition of pegcetacoplan (C3 inhibitor) as bridging therapy pending suppression of his plasma cell clone. Outcomes are currently being monitored.
Discussion
Emerging data suggest a link between monoclonal gammopathies and complement dysregulation; clinical significance and therapeutic implications remain uncertain. This case presents a novel use of adjunctive direct complement inhibition with clone-directed therapy in the management of refractory HCDD with evolving evidence of complement activity.