Treatment algorithm – Limited stage Gastric Marginal Zone Lymphoma Diagnosis: – Histology including appropriate B-cell immunohistochemical panel and staining for Helicobacter pylori – FISH for t(11;18) Staging tests – If immunohistochemistry for Helicobacter pylori negative, test for H. pylori according to local policy (serology, urea breath test, or stool antigen test) – CT chest/abdomen/pelvis (role of PET-CT unclear at this stage and should be used in the context of clinical trials only) – BM biopsy only indicated in symptomatic advanced stage disease when treatment is indicated Page 1 of 3, Agreed MCCN Haematology CNG, January 2013

Helicobacter pylori positiveHelicobacter pylori negative First lineHelicobacter pylori eradication (consider a second course if needed) Radiotherapy (30-40Gy) 2 nd lineRadiotherapy (30-40Gy)Rituximab 3 rd lineRituximabR-chemo* 4 th lineR-chemo* Treatment algorithm – Limited Stage Gastric Marginal Zone Lymphoma All patients should be considered for, and offered, NCRI/MRC clinical trials at diagnosis and relapse Notes: Please also see the following slide on follow-up Patients with t(11;18) are unlikely to respond to H. pylori eradication and early consideration should be given to other strategies. Histological lymphoma regression following H. pylori eradication can take >12 months Gastrectomy is associated with high morbidity and is not demonstrably superior to radiotherapy in terms of efficacy. There are no data at present to support the use of additional therapy in patients who achieve clinical and endoscopic disease clearance, but remain positive on histology or clonality studies. *There are no comparative data at present to recommend one cytotoxic drug over another. R-Chlorambucil offers superior response rates to Chlorambucil alone, though with no difference in overall survival 1. Fludarabine based therapy appears to offer high response rates, though with apparently greater toxicity 2. For patients with symptomatic advanced stage disease, a reasonable approach would be to offer first-line therapy as per Follicular lymphoma. Page 2 of 3, Agreed MCCN Haematology CNG, January 2013

References: 1.Zucca E, et al. Blood 2010; 116: 432 (abstract) 2.Brown JR, et al. Br J Haem 2009; 145: NCCN Guidelines version , Last accessed 14/8/2012http:// 4.Zucca E, Dreyling M. Ann Oncol 2010; 21 (Supplement 5): v175 Treatment algorithm – Limited stage Gastric Marginal Zone Lymphoma Prepared by Dr A Arumainathan, August 2012 Page 3 of 3, Agreed MCCN Haematology CNG, January 2013 Follow-up: A stool antigen test or breath test should be performed 4 weeks after H.pylori therapy to demonstrate successful eradication. Follow-up endoscopy (with multiple biopsies) should be performed 3 months after any line of therapy. Asymptomatic patients who remain H.pylori positive on follow-up biopsy should be given a second course of eradication therapy Endoscopic follow-up thereafter is left at clinicians’ discretion, but a suggested regimen is annually for the first 2 years, and then guided by symptoms.