Kalpadakis, Christina

Abstract Background: The salivary gland is one of the most common sites of involvement by non-gastric extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). This multicenter, international trial sought to characterize the clinical course, treatment and outcome of patients with salivary gland MALT lymphoma. Methods: Patients were identified from multiple international sites including the Mayo Clinic Lymphoma Database (n=89), three International Extranodal Lymphoma Study Group (IELSG) cohorts (n=138), and the University of Athens (n=21). All patients had biopsy-confirmed MALT lymphoma of the salivary gland by WHO criteria. Clinical characteristics, treatment, and outcomes were obtained from the respective patient databases. Survival probability was estimated using the Kaplan-Meier method and compared between groups with the Wilcoxon or log-rank. The impact of variables on survival was assessed by the Cox proportional hazards model. Results: Patients and clinical features: From 1983 to 2012, 247 patients with MALT lymphoma were included. Clinical characteristics are shown in Table 1. The median age at diagnosis was 59, and the male-to-female ratio was 1:3. The majority of patients (76%) presented with limited stage disease, and the parotid gland was the most common site of involvement (78%). There was a history of antecedent autoimmune disease in 41% of patients, and Sjögren’s disease was the most common (83%). Treatment: Information on initial treatment was available on 242 patients. 137/242 patients (57%) initially received local therapy with either surgery (n=81), radiation (n=26), or both (n=30). Of these, 25 received adjuvant systemic therapy. 90/242 patients (37%) were treated initially with systemic therapy, of whom 54% had localized and 46% had stage IV disease. Rituximab was used alone (n=16) or in combination with chemotherapy (n=26) in 42 of the 90. 15/242 patients (6%) were initially observed. Survival: The median OS for all patients was 18.3 years. PFS following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first line for all patients, or for those with stage I or II disease. On univariate analysis age <60, stage, IPI, normal LDH, the presence of Sjögren’s disease, and treatment with rituximab were associated with improved overall survival. Age <60, low to intermediate IPI and normal LDH were associated with improved PFS. On multivariate analysis, age<60, and IPI were associated with improved OS and PFS and Sjögren’s disease was associated with improved OS. Relapse/progression: The site of progression was known in 51 of 76 patients who progressed. 15 (29%) patients progressed in the same salivary gland or regional nodes; in 16 (21%) recurrence involved the contralateral salivary gland; 20 (31%) had distant progression. Relapse histology was identified in 30. The most common pathology at relapse was MALT (n=28), with one patient progressing to diffuse large B-cell lymphoma. A second patient developed a mantle cell lymphoma. Conclusions: Salivary gland MALT lymphoma commonly presents at an early stage, and has a favorable prognosis with a median OS of 18 years. Surgical or radiation therapy does not appear to have benefit over systemic therapy. Patients with Sjögren’s disease appear to have a better survival. The role of rituximab and optimal first-line therapy should be evaluated further in prospective trials. Table 1: Characteristics of 247 patients with salivary MALT Characteristic N (%) Age, median; range 59; 18-93 Sex, Male: Female 62: 185 (25: 75) Primary site of involvement Parotid 193 (78) Submandibular 12 (5) Other/not specified 42 (17) Extent (unilateral: bilateral) 89:21 Missing data 137 Autoimmune disorder* 101(41) Sjögren’s 84 (33) Rheumatoid arthritis 9 (4) Raynaud’s phenomenon 8 (3) Scleroderma 5 (2) Other 19 (8) Stage IE 147 (59) IIE 42 (17) IV 56 (23) Missing data 2 (1) IPI Score Low (0-1) 126 (51) Low-Intermediate (2) 20 (8) High-intermediate (3) 21 (8) High (4-5) 5 (2) Missing data 75 (31) Elevated LDH 17 (7) ECOG PS 0-1 246 2 1 Extranodal sites 1 58 (23) 2 187 (76) Missing data 2 (1) B symptoms 9 (4) * Percents may not equal 100 as some patients had more than one disorder. Figure One: Overall survival of patients with and without Sjögren’s disease Figure One:. Overall survival of patients with and without Sjögren’s disease Disclosures Nowakowski: Celgene, Morphosis: Consultancy. Zucca:Roche, Mundipharma, Novartis, Jannsen, Celgene: Consultancy, Honoraria, Research Funding.

Abstract Background. The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). A large series of patients with long-term follow-up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. Methods. Patients with biopsy-confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long-term outcomes were evaluated. Results. A total of 247 patients were evaluated; 76% presented with limited-stage disease. There was a history of autoimmune disorder in 41%, with Sjögren disease being the most common (83%). Fifty-seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression-free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first-line management. On multivariate analysis, age &lt;60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjögren disease was associated with improved OS. Conclusion. Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjögren disease have improved survival. Risks for long-term complications must be weighed when determining initial therapy. Implications for Practice: Patients with salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) have an excellent prognosis, particularly those with associated Sjögren's disease. A wide range of available therapies may provide similar durable rates of disease control and survival. Therefore, an important goal in selection of therapy should be to minimize morbidity from treatment. When determining initial therapy for these patients, practitioners should consider the potential side effects and long-term toxicities of treatment.