A Segarra1, K V Arredondo2, J Jaramillo2, E Jatem1, M T Salcedo3, I Agraz4, N Ramos4, C Carnicer5, N Valtierra5, E Ostos5. 1. Department of Nephrology, University Hospital Arnau of Vilanova, Biomedical Research institute of Lleida, University of Lleida, Spain. 2. Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Department of Pathology, Hospital Universitario Vall d'Hebron, Barcelona, Autonomous University of Barcelona, Spain. 4. Department of Nephrology, University Hospital Vall d'Hebron, Barcelona, Autonomous University of Barcelona, Spain. 5. Department of Biochemistry, University Hospital Vall d'Hebron, Barcelona, Autonomous University of Barcelona, Spain.
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.
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.
Authors: Sarika Chaudhari; Grace S Pham; Calvin D Brooks; Viet Q Dinh; Cassandra M Young-Stubbs; Caroline G Shimoura; Keisa W Mathis Journal: Front Physiol Date: 2022-06-13 Impact factor: 4.755
Authors: Tomas Walhelm; Iva Gunnarsson; Rebecca Heijke; Dag Leonard; Estelle Trysberg; Per Eriksson; Christopher Sjöwall Journal: Front Immunol Date: 2021-10-01 Impact factor: 7.561