OBJECTIVES: The overexpression of B-cell activating factor (BAFF) in mucosa-associated lymphoid tissue (MALT) may decrease the efficacy of rituximab treatment in Sjögren's syndrome (SS). Anti-CD20 therapy was effective on marginal zone B cells, in the murine model for human CD20 expression only when preceded by anti-BAFF therapy. The possible efficacy of a sequential anti-BAFF/anti-CD20 therapy in SS was investigated. METHODS: We treated with belimumab, a monoclonal anti-BAFF antibody, and soon after with rituximab a patient with severe, refractory SS, parotid low-grade B-cell MALT lymphoma and cryoglobulinaemic vasculitis. Previous treatments with rituximab and with rituximab plus high dose glucocorticoids, as well as with cyclophosphamide, azathioprine, plasma exchange, hyperbaric therapy, VAC therapy, prostacyclin, mycophenolate mofetil and surgery, had previously failed. Treatment with belimumab was then given, but it also failed. A new course of rituximab (375 mg/m2; four weekly infusions) was started 49 days after the last infusion of belimumab. RESULTS: This sequential belimumab-rituximab treatment was followed by a marked amelioration, with the complete and persistent regression of lymphoma and healing of a refractory skin ulcer. A full cycle of rituximab was then repeated 6 and 12 months later; no further treatment was given in the following 22 months up to now. Serum cryoglobulins and rheumatoid factor became persistently negative and serum BAFF and C4 persistently normal. No relevant side effects were noticed, except for a marked decrease in serum IgM. The follow up after belimumab-rituximab sequential therapy is now three and a half years. CONCLUSIONS: Therapy with belimumab followed by rituximab may be effective for SS-related B-cell lymphoproliferation. The efficacy and safety of the sequential or concomitant targeting of BAFF and CD20 deserves further evaluation in SS.
OBJECTIVES: The overexpression of B-cell activating factor (BAFF) in mucosa-associated lymphoid tissue (MALT) may decrease the efficacy of rituximab treatment in Sjögren's syndrome (SS). Anti-CD20 therapy was effective on marginal zone B cells, in the murine model for humanCD20 expression only when preceded by anti-BAFF therapy. The possible efficacy of a sequential anti-BAFF/anti-CD20 therapy in SS was investigated. METHODS: We treated with belimumab, a monoclonal anti-BAFF antibody, and soon after with rituximab a patient with severe, refractory SS, parotid low-grade B-cell MALT lymphoma and cryoglobulinaemic vasculitis. Previous treatments with rituximab and with rituximab plus high dose glucocorticoids, as well as with cyclophosphamide, azathioprine, plasma exchange, hyperbaric therapy, VAC therapy, prostacyclin, mycophenolate mofetil and surgery, had previously failed. Treatment with belimumab was then given, but it also failed. A new course of rituximab (375 mg/m2; four weekly infusions) was started 49 days after the last infusion of belimumab. RESULTS: This sequential belimumab-rituximab treatment was followed by a marked amelioration, with the complete and persistent regression of lymphoma and healing of a refractory skin ulcer. A full cycle of rituximab was then repeated 6 and 12 months later; no further treatment was given in the following 22 months up to now. Serum cryoglobulins and rheumatoid factor became persistently negative and serum BAFF and C4 persistently normal. No relevant side effects were noticed, except for a marked decrease in serum IgM. The follow up after belimumab-rituximab sequential therapy is now three and a half years. CONCLUSIONS: Therapy with belimumab followed by rituximab may be effective for SS-related B-cell lymphoproliferation. The efficacy and safety of the sequential or concomitant targeting of BAFF and CD20 deserves further evaluation in SS.
Authors: Ruoyi Jiang; Miriam L Fichtner; Kenneth B Hoehn; Minh C Pham; Panos Stathopoulos; Richard J Nowak; Steven H Kleinstein; Kevin C O'Connor Journal: JCI Insight Date: 2020-07-23
Authors: J Wild; B J Schmiedel; A Maurer; S Raab; L Prokop; S Stevanović; D Dörfel; P Schneider; H R Salih Journal: Leukemia Date: 2015-02-24 Impact factor: 11.528
Authors: Luca Quartuccio; Alessandra Bortoluzzi; Carlo Alberto Scirè; Antonio Marangoni; Giulia Del Frate; Elena Treppo; Laura Castelnovo; Francesco Saccardo; Roberta Zani; Marco Candela; Paolo Fraticelli; Cesare Mazzaro; Piero Renoldi; Patrizia Scaini; Davide Antonio Filippini; Marcella Visentini; Salvatore Scarpato; Dilia Giuggioli; Maria Teresa Mascia; Marco Sebastiani; Anna Linda Zignego; Gianfranco Lauletta; Massimo Fiorilli; Milvia Casato; Clodoveo Ferri; Maurizio Pietrogrande; Pietro Enrico Pioltelli; Salvatore De Vita; Giuseppe Monti; Massimo Galli Journal: Clin Rheumatol Date: 2022-09-28 Impact factor: 3.650
Authors: Benjamin A Fisher; Colin C Everett; John Rout; John L O'Dwyer; Paul Emery; Costantino Pitzalis; Wan-Fai Ng; Andrew Carr; Colin T Pease; Elizabeth J Price; Nurhan Sutcliffe; Jimmy Makdissi; Anwar R Tappuni; Nagui S T Gendi; Frances C Hall; Sharon P Ruddock; Catherine Fernandez; Claire T Hulme; Kevin A Davies; Christopher John Edwards; Peter C Lanyon; Robert J Moots; Euthalia Roussou; Andrea Richards; Linda D Sharples; Michele Bombardieri; Simon J Bowman Journal: Ann Rheum Dis Date: 2017-12-23 Impact factor: 19.103