Rituximab therapy for systemic manifestations and MALT lymphomas of the parotid gland in Sjögren's disease: Preliminary data


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AIM: To evaluate the efficacy of rituximab (RT) in cryoglobulinemic vasculitis (CGV) and MALT lymphomas of the parotid gland (PG) in patients with Sjögren's disease (SD). /MATERIAL AND METHODS: RT therapy was performed in 13 patients with SD and CGV and in 17 with SD and PG MALT lymphoma. Eleven patients with SD received RT monotherapy and 19 with this disease had combined therapy with RT and cyclophosphan (CP). RT was used intravenously dropwise at a dose of 500 mg weekly or once every two weeks in combination with intravenous dropwise CP 1000 mg the next day with 4-6 per course. For the diagnosis of MALT lymphomas, all the patients with SD underwent incisional PG biopsy under local anesthesia at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. PG biopsy specimens were histologically and immunohistochemically studied at the Russian Cancer Research Center, Russian Academy of Medical Sciences. In 11 cases, B-cell clonality was identified from immunoglobulin (Ig) heavy chain genes rearrangements, by using polymerase chain reaction at the Hematology Research Center, Ministry of Health and Social Development of the Russian Federation /RESULTS: Cutaneous manifestations of vasculitis disappeared in 75% of cases after monotherapy with RT and in 100% of cases after combination therapy with RT and CP. At 6-month follow-up, a complete response to therapy remained in 25% of the patients after a course of monotherapy and in 83% after combined therapy. Serum monoclonal Ig cryoglobulins and their urinary light chains ceased to be detectable in 75% of the patients in both groups at 3 months. At 6 months, a recurrence of mixed monoclonal cryoglobulinemia was seen in 50 and 43% of cases after monotherapy and combined therapy, respectively. The clinical and laboratory response of cryoglobunemic glomerulonephritis to combined therapy with RT and CP was complete in 60% of cases at 6-month follow-up. After RT monotherapy, the patients with SD and PG MALT lymphoma achieved a complete clinical response in 88%, of whom histological and immunohistochemical reexaminations of PG biopsy specimens revealed no signs of MALT lymphoma in 71% of cases. B-cell clonality remained in the PG biopsy specimens following RT monotherapy. After the combination of RT and CP, a complete clinical response to therapy was observed in 100% of the patients, a complete histological response and a complete molecular one were seen in 83 and 60%, respectively /CONCLUSION: RT showed its efficacy in treating SD patients with CGV and PG MALT lymphomas.

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Терапия ритуксимабом системных проявлений и MALT-лимфом околоушных слюнных желез при болезни Шегрена (предварительные данные). - Резюме. Цель исследования. Оценить эффективность ритуксимаба (РТ) при криоглобулинемическом васкулите (КГВ) и MALT-лимфомах околоушных слюнных желез (ОУЖ) у больных болезнью Шегрена (БШ). Материалы и методы. Терапию РТ проводили 13 больным БШ с КГВ и 17 больным БШ с MALT-лимфомой ОУЖ. Монотерапию РТ получили 11 и комбинированную терапию РТ и ЦФ - 19 больных БШ. РТ назначали по 500 мг внутривенно капельно еженедельно или 1 раз в 2 нед в комбинации с 1000 мг циклофосфана (ЦФ) внутривенно капельно на следующий день, на курс 4-6. Для диагностики MALT-лимфом всем больным БШ в НИИ ревматологии РАМН проводили инцизионную биопсию ОУЖ под местной анестезией. Биоптаты ОУЖ исследовали в РОНЦ РАМН гистологическим и иммуногистохимическим методами. В 11 случаях в биоптатах ОУЖ определялась В-клеточная клональность по реаранжировке генов тяжелых цепей Ig методом полимеразной цепной реакции в ФГБУ ГНЦ Минздрава РФ. Результаты. Кожные проявления васкулита исчезли в 75% случаев после монотерапии РТ и в 100% случаев после комбинированной терапии РТ и ЦФ. К 6-му месяцу наблюдения полный ответ на терапию сохранялся у 25% больных после курса монотерапии и у 83% пациенток после комбинированного курса. Криоглобулины, моноклональные Ig в сыворотке крови и их легкие цепи в моче перестали определяться к 3-му месяцу у 75% больных в обеих группах. Рецидив смешанной моноклональной криоглобулинемии к 6-му месяцу был в 50% случаев после монотерапии и в 43% - после комбинирован­ной терапии. Клинико-лабораторный ответ криоглобулинемического гломерулонефрита на комбинированную терапию РТ и ЦФ в 60% случаев к 6-му месяцу наблюдения был полным. При монотерапии РТ больных БШ с MALT-лимфомой ОУЖ у 88% достигнут полный клинический ответ, из которых при повторном гистологическом и иммуногистохимическом исследовании биоптатов ОУЖ признаков MALT-лимфомы не обнаруживалось в 71% случаев. В-клеточная клональность сохранялась в биоптатах ОУЖ после монотерапии РТ. При комбинации РТ и ЦФ полный клинический ответ на терапию наблюдался у 100% больных, полный гистологический ответ - у 83% и полный молекулярный ответ - у 60%. Заключение. Показана эффективность РТ у больных БШ с КГВ и MALT-лимфомами ОУЖ.
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