Efficacy and safety of bortezomib in refractory lupus nephritis: a single-center experience. (February 2020)

• Record Type: Journal Article
• Authors: Segarra, A; Arredondo, K V; Jaramillo, J; Jatem, E; Salcedo, M T; Agraz, I; Ramos, N; Carnicer, C; Valtierra, N; Ostos, E
• Is Part Of: Lupus. Volume 29:Number 2(2020)
• Page Start: 118
• Page End: 125
• Publication Date: 2020-02
• Subjects: Lupus nephritis -- bortezomib -- refractory lupus nephritis -- proteasome inhibitor; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1177/0961203319896018
• Languages: English
• ISSNs: 0961-2033

Abstract

Background and Objectives: Resistant lupus nephritis (LN) has been associated with the persistence of long-lived plasma cells. Preliminary studies identified bortezomib as a potential treatment option for patients with refractory LN. The aim of this study was to analyze the efficacy and safety of bortezomib in the treatment of severe refractory LN. Methods: This retrospective study included 12 female patients diagnosed for the first time with class IV or IV/V LN with acute or rapidly progressive kidney injury ( n = 11) and/or severe nephrotic syndrome ( n = 1) who showed resistance to induction therapy with cyclophosphamide, steroids, mycophenolate, and rituximab, and were treated with either intravenous or subcutaneous bortezomib plus intravenous dexamethasone. Results: All patients with acute or rapidly progressive kidney injury showed a significant reduction in both biochemical and immunological activity after a mean of 6 (minimum 5, maximum 7) weekly cycles of bortezomib regimen, with a significant increase in C3 levels and a significant decrease of anti-ds DNA antibody titers, Systemic Lupus Erythematosus Disease Activity Index score, serum creatinine, and proteinuria. One patient (8.3%) achieved a complete response, and 10 patients (83.4%) achieved a partial response. During follow-up, all these patients maintained partial responses under treatment with mycophenolate and low-dose glucocorticoids. The patient with refractory nephrotic syndrome showed a partial response but relapsed 11 months after the end of bortezomib treatment and was resistant to treatment. A significant decrease in serum IgG levels after initiation of bortezomib treatment was observed in all patients, five of them (41.6%) showed hypogammaglobulinemia (<500 mg/dl), but no patient suffered from opportunistic infections; in only two patients (16.6%) hypogammaglobulinemia persisted at the end of follow-up. Two patients (16.6%) suffered from sensory neuropathy, which led to bortezomib treatment discontinuation. Conclusions: Bortezomib may be an effective option for refractory LN, but close monitoring must be performed for possible adverse events such as peripheral neuropathy and hypogammaglobulinemia.