FRI0214 EFFICACY OF RITUXIMAB AND CYCLOPHOSPHAMIDE TREATMENT IN PATIENTS WITH PRIMARY SJOGREN’S SYNDROME AND PAROTID GLAND MALT LYMPHOMA
Authors: Anna Torgashina, Bogdan Chalcev, Evgeniya Sokol, Vladimir Vasiliev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Mucosa-associated lymphoid tissue (MALT) lymphoma occurred in a higher frequency and at an earlier age in primary Sjögren's syndrome (pSS) than reported for MALT lymphoma in the general population. The optimal treatment of MALT lymphoma in pSS has not been defined. Objectives: to analyze retrospectively the long-term clinical course of pSS in patients with MALT lymphoma. <h3>Methods:</h3> 63 SS patients with MALT lymphoma were retrieved from our pSS database. Most of the 63 pSS-lymphoma patients were female (n=60; 95%). pSS was diagnosed at a mean age of 51 (43-58) years and lymphoma at a mean of 7 (2-10) years later. Total mean follow-up was 5 years (2-8). 14 patients received immunomodulator agents for SS before the development of lymphoma (low doses of prednisone - 8 patients, <b>chlorambucil</b> – 7, cyclophosphamide – 3 patients). In 43 patients, the diagnosis of SS and MALT - lymphoma were established simultaneously. Clinical features and treatment outcome of MALT - lymphoma as well as SS activity was evaluated. All patients had features of autoimmune disease (ANA-100%, RF-90%, anti-Ro or/and anti-La antinuclear antibodies-94%) and met the diagnostic criteria of the Association of Rheumatologists of Russia for primary Sjogren's syndrome: salivary gland involvement (stimulated parotid flow rate &lt; 2,5 ml in 5 min, parotid sialography showing the presence of diffuse punctuate or globular shadows with a diameter &gt; 1mm., histopathology: a focus score&gt;2 per 4mm2 in minor salivary gland biopsy), keratoconjunctivitis sicca (stimulated Schirmer's test &lt;10mm in 5 min, tear break-up time &lt; 10 seconds, rose Bengal test or fluorescent test&gt;1+), presence of abnormal concentrations of at least one of the serum autoantibodies (anti-Ro, anti-La, antinuclear antibodies, IgM-rheumatoid factor). The histologic and immunohistochemical diagnosis of lymphoma was performed with B-cell clonality determination in salivary gland tissue. Patients were treated with RTX (25 patients) or RTX+CPH (38 patients). Patients received 2 1g intravenous infusions of RTX 2 weeks apart, then 375 mg every 3 months for 2 years. Cyclophosphamide 1000 mg was administered every two weeks for a period of 12 weeks. <h3>Results:</h3> MALT lymphoma was localized in parotid glands in 60 cases, submandibular salivary glands – in 2 cases, lacrimal gland – in 1 case. Eleven patients showed systemic features (7-purpura, 1-peripheral neuropathy, 3 – nephritis). Blood serum and urine examination revealed monoclonal secretion in 16/56 patients (7-IgMk, 4-IgGk and IgG, 2-IgAk and 3 - BJk). Nineteen of 56 (34%) patients had cryoglobulinaemia. After follow-up of 24 mo, complete clinical remission (CR) of MALT lymphoma (normalization of salivary gland size, disappearance of lymphadenopathy and cytopenia) was obtained in 25 (72%) in the group of RTX and 35 (92%) in the group of RTX+CPH (p=0.05). An incision biopsy of the parotid gland before and after therapy was made in 21 patients. Complete disappearance of histological pattern of MALT lymphoma was shown in 50% of the RTX treated patients and in 66% patients with combined therapy. B-cell clonality in parotid glands disappeared in 3/5 cases after RTX monotherapy and in 1/4 cases after RTX with CPH therapy. Cryoglobulinaemia disappeared in 33% patients in group of RTX and 46% in group of RTX+CPH (p=0.6). <h3>Conclusion:</h3> Complete clinical remission of the lymphomas was achieved significantly more often in the group treated with RTX plus cytostatic agent in comparison with patients who had RTX monotherapy. <h3>Disclosure of Interests:</h3> None declared