MALT LYMPHOMA. Silvia Montoto, St Bartholomew s Hospital, London, UK ESMO Preceptorship on Lymphoma
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1 MALT LYMPHOMA Silvia Montoto, St Bartholomew s Hospital, London, UK ESMO Preceptorship on Lymphoma Madrid, November 2016
2 Disclosuresof commercial support Roche Gilead
3 Marginal zone B-cell lymphomas SMZL, NMZL, MALT The NHL Classification Project, Blood 1997
4 The Mucosa Associated Lymphoid Tissue concept Native MALT normally present in certain extra-nodal sites (e.g., Peyer s patches) Acquired MALT where lymphoid tissue is not a natural component (e.g.,sjögren, Hashimoto, H. pylori-gastritis) MALT Lymphoma first described in the stomach by Isaacson and Wright in 1983, but can arise from a wide variety of extra-nodal tissues (usually at acquired MALT sites)
5 MALT lymphoma: clinicalcharacteristics Median age: 60 years BM involvement: 15-20% Most common: gastric(1/3) Other sites of involvement: Small bowel/colon Lung Ocular Skin Thyroid Salivary glands
6 Gastric MALT 50% of primary gastric lymphoma Associated with HP infection(2/3) Molecular characteristics: t(11;18)(q21;q21) Potential histological transformation to a highgrade lymphoma
7 H. pylori and MALT lymphoma B B B B B B B B B H. pylori-dependent MALT lymphoma neutrophilsactivation with release of genotoxic free radicals H. pylori-independent MALT lymphoma genetic alterations B B B B B B additional genetic damages B B-cell proliferation H. pylori chronic gastritis contact-dependent B-cell stimulation antigen selection autoimmunity T T T T T mucosal T-cell proliferation diffuse large B-cell lymphoma
8 Diagnosis and staging of gastric MALT OGD nonspecific gastritis peptic ulcer rarely mass lesions often multifocal (even if macroscopically normal) FISH Echo-endoscopy H pylori detection CAP CT BM aspirate and biopsy
9 Detection of Helicobacter pylori Test Sensitivity Specificity Advantages Disadvantages Histology: H/E, IHC Histology: urease test (Clo-test) Histology: culture 95% 99% Information re gastric histo Interobserver variability; affected by PPI/ATB use 90% 93% Rapidresults Affected by PPI/ATB use 58% 100% ATBsensitivity Trained staff; expensive Serology 76-84% 79-90% Widely available; inexpensive Urea breath test >95% >95% Useful before/after treatment Stool Ag test 96% 97% Useful before/after treatment +vemight reflect past infection; not useful after treatment False veif PPI/ATB; personnel/resources Stool collection; false veif PPI/ATB;
10 Gastric MALT-Staging Zuccaet al, Annals of Oncol, 2013
11 Gastric MALT lymphoma: OS according to treatment Treatment n CR rate 5-year OS Antibiotics 45 67% 94% Local treatment a % 91% Chemotherapy 8 50% 75% Combined modality b 5 100% 80% Total 72 74% 89% a surgery ± RT, b surgery + adjuvant chemotherapy Pinotti et al, 1997
12 Surgery for gastric MALT Surgery +/- additional treatment (chemo, RT): 5-year OS: 85%-95% Total gastrectomy should be considered since MALT lymphoma is often multifocal
13 Radiotherapy for gastric MALT Author n RT dose (Gy) FFP Schechter, % at 2 yr Tsang, % at 5 yr Yahalom, median 89% at 4 yr Hitchcock, median 78% (100% local)
14 Chemotherapy for MALT Single Agent ORR CR Reference alkylating 100% 75% Hummel, JCO 1995 cladribine 100% 84% Jager, JCO 2002 oxalyplatin 93% 56% Raderer, JCO 2005 Combination CVP 100% 100% Zinzani, Cancer 2004 FM 100% 100% Zinzani, Cancer 2004 MCP 100% 53% Wohrer, Ann Oncol 2003
15 Response to antibiotics Reference n staging CR rate time to CR relapses procedure (%) (mos.) (n) Savio, CT Pinotti, CT Neubauer, CT±EUS Nobre Leitao, CT+EUS Steinbach, CT±EUS Montalban, CT±EUS Ruskone-Formestraux, CT+EUS LY03 interim analysis, CT
16 Predictive factors for lack of response to antibiotics Deep infiltration of gastric wall Lymph node involvement Increased number of large cells t(11;18)
17 ESMO guidelines: localised stage
18 ESMO guidelines: advanced stage
19 IELSG 19 study
20 IELSG 19 study Zuccaet al, J ClinOncol, 2013
21 Assessment of response Histology& assessment of HP eradication Persistence of residual lymphoma on Bx can last 12 months PCR for B-cell clonality remains +ve in 50% of histological CR
22 Follow-up EGILS 2011 guidelines follow-up gastroscopies with biopsies seem advisable ESMO 2013 guidelines a long-term careful endoscopic and systemic follow-up is recommended for all patients
23 Histological transformation in MZL 340 patients with MZL 46% MALT 25% SMZL 11% NMZL 18% CBL-MZL HT Bx-proven Median follow-up: 5 yrs Conconi et al, Annals Oncol, 2015
24 Non-gastric MALT
25 Non-gastric MALT Chlamydia psittaci v Sjögren syndrome Borrelia burgdorferi Hashimoto thyroiditis
26 Non-gastric MALT: outcome according to primary site Zucca et al, Blood, 2003
27 MALT of the salivary glands: IELSG patients with MALT Median follow-up: 55 months Jackson et al, The Oncol, 2015
28 OAL and Chlamydia: IELSG 27 48% eradication RR: 65% Ferreri et al, J Clin Oncol, 2012
29 Summary Antigen-driven processes treatment of initiating event Disseminated disease, limited to mucosal sites, not associated with poor outcome Excellent prognosis (OS) regardless of treatment
30 Thank you!
31 Pathogenesis rare, 2% t(1;14) BCL10 deregulation common, 35% t(11;18) API2/MALT1 fusion at non-gi sites, 20% t(14;18) MALT 1 deregulation NF-kB activation Antibiotic-resistant gastric MALT lymphoma
32 Alkylating agents for MALT 24 patients, 17 stage I, 7 stage IV Cyclophosphamide or Chlorambucil for 8-24 mos. 100%ORR (75%CR) 5-year EFS: 50% 5-year OS: 75% 5 relapses at initial sites (1with transformation) Hammel et al. JCO, 1995
33 C psittaci in Ocular Adnexae Lymphoma (OAL) Orbital Lymph Chlamydia OAL biopsies node P-value (n= 40) (n= 20) (n= 26) psittaci 32 (80%) 0 3 (12%) trachomatis ns pneumoniae ns Objective response following doxycycline: 48% (6/27: CR, 7/27: PR) Ferreri et al, JNCI, 2006
34 Non-gastric MALT Zucca et al. Blood, 2003
35 IELSG study of non-gastric MALT lymphoma N: 180 (68M/ 112F, median age: 59 yrs) PS>2: 4% B-symptoms: 3% Bone marrow involvement: 14% Nodal involvement: 21% More than 1 extra-nodal: 23% Stage IV: 27%
36 OAL and Chlamydia: IELSG 27 Reference Country No. of Assessed Cases Frequency of Positive Cases Ferreri 2004 Italy 40 80% You 2005 Korea 33 79% Gracia 2006 Cuba 20 5% Vargas 2005 USA 7 0% Daibata 2006 Japan 18 0% Rosado 2005 USA 49 0% Mulder 2006 Nederlands 20 0% Zhang 2005 USA 15 0% Zucca and Bertoni, JNCI, 2006
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