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Abstract: SA-PO0192

Daratumumab: A Key to Successful Renal Outcomes in Monoclonal Gammopathy

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Author

  • Roy, Gargi, Beaumont Hospital, Dublin, Ireland
Introduction

Renal survival outcomes in monoclonal gammopathies have improved with the use of clone-directed therapy. Daratumumab (Dara), a CD38-specific monoclonal antibody, has emerged as one such novel agent. We describe a case of immunoglobulin light-chain (AL) amyloidosis, followed by a rare case of myeloma-associated C3 glomerulopathy (C3G), both of whom achieved complete remission and improved kidney function following treatment with Dara.

Case Description

Case 1:
A 61-year-old female with psoriasis presented with nephrotic syndrome (Urine PCR>3031mg/dL, Creatinine 288 umol/L). Serum immunofixation identified an IgG lambda paraprotein. Renal biopsy confirmed lambda-subtype AL amyloidosis. Initial treatment with bortezomib, cyclophosphamide and dexamethasone (VCD) failed to achieve clonal response. Second-line lenalidomide-dexamethasone was discontinued due to thromboembolic adverse effects. Single-agent Dara was then trialled to maximise amyloid remission pre-transplant. This was given weekly (1800mg subcutaneously on non-dialysis days) for eight cycles, and monthly thereafter. Following eight doses, paraprotein levels were undetectable and free light chain ratio had normalised. She received a living-related donor kidney transplant one year later. Dara was not recommenced post-transplant due to complete remission. To date, graft function has remained intact (creatinine 80umol/L).

Case 2:
A 42-year-old male with smouldering multiple myeloma presented with a lower limb vasculitic rash, bone pains and nephrotic syndrome (creatinine 369umol/L, urine PCR 437mg/dL). Renal biopsy demonstrated focal segmental membranoproliferative glomerulonephritis with C3 deposition. Bone marrow aspirate showed 80% plasma cells, consistent with transformation to multiple myeloma. A diagnosis of C3G was made. One cycle of Dara-VCD reduced proteinuria to 20mg/dL. Complete remission was achieved following four cycles. The patient underwent successful autologous stem cell transplant (ASCT) and now maintains normal renal function (creatinine 96umol/L).

Discussion

Renal AL amyloidosis and C3G have historically been associated with poor prognosis. In our case series, treatment with Dara enabled successful kidney transplantation and ASCT in these two distinct haematological entities, respectively. Prospective studies should explore the efficacy of anti-CD38 antibodies in the first-line treatment of monoclonal gammopathy-associated renal failure.

Digital Object Identifier (DOI)