Post on 30-Apr-2020
Silvia Montoto, St Bartholomew’s Hospital, London, UKESMO Preceptorship on Lymphoma
Lugano, 3-4 November 2017
MALT LYMPHOMA
Disclosures:• Roche: honoraria• Gilead: travel grant
ESMO Preceptorship on LymphomaLugano, 3-4 November 2017
Marginal zone B-cell lymphomas
The NHL Classification Project, Blood 1997
SMZL, NMZL, MALT
The Mucosa Associated Lymphoid Tissue concept
• Native MALTnormally present in certain extra-nodal sites (e.g. Peyer’s patches)
• Acquired MALTwhere lymphoid tissue is not a natural component (e.g. Sjögren, Hashimoto, H. pylori-gastritis)
• MALT Lymphoma1st described in the stomach by Isaacson and Wright in 1983; it can arise from a wide variety of extra-nodal tissues (usually at acquired MALT sites)
MALT lymphoma: clinical characteristics
• 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
Gastric MALT
• 50% of primary gastric
lymphomas
• Associated with HP
infection (2/3)
• Molecular characteristics:
t(11;18)(q21;q21)
• Potential histological
transformation to a ‘high-
grade’ lymphoma
H. pylori and MALT lymphoma
BB
B
B
B B TT
mucosal T-cell proliferation
H. pylori-dependentMALT lymphoma B-cell proliferation
contact-dependent B-cell stimulation
neutrophils activation with release of
genotoxic free radicals
antigen selectionautoimmunity
geneticalterations
T
additional genetic damages
B
T
T
diffuse large B-cell lymphoma
H. pylori chronic gastritis
H. pylori-independentMALT lymphoma
B
B B
B
B
B B
B
B
B
Diagnosis and staging of gastric MALT
• OGD + biopsies– 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
Detection of Helicobacter pylori
Test Sensitivity Specificity Advantages Disadvantages
Histology: H/E, IHC
95% 99% Information re gastric histo
Interobservervariability; affected by PPI/ATB use
Histology: urease test (Clo-test)
90% 93% Rapid results Affected by PPI/ATB use
Histology: culture
58% 100% ATB sensitivity Trained staff; expensive
Serology 76-84% 79-90% Widely available; inexpensive
+ve might reflect past infection; not useful after treatment
Urea breath test >95% >95% Useful before/after treatment
False –ve if PPI/ATB; personnel/resources
Stool Ag test 96% 97% Useful before/after treatment
Stool collection; false –ve if PPI/ATB;
Gastric MALT-Staging
Zucca et al, Annals of Oncol, 2013
Gastric MALT lymphoma: OS according to treatment
Treatment n CR rate 5-year OS
Antibiotics 45 67% 94%
Local treatmenta 14 100% 91%
Chemotherapy 8 50% 75%
Combined modalityb 5 100% 80%
Total 72 74% 89%
asurgery ± RT, bsurgery + adjuvant chemotherapy
Pinotti et al, 1997
Surgery for gastric MALT
• Surgery +/- additional treatment (chemo,RT): 5-year OS: 85%-95%
• If surgery is considered total gastrectomy(as MALT lymphoma is often multifocal)
Radiotherapy for gastric MALT
Author n RT dose (Gy) FFP
Schechter, 1998 17 28-43 100% at 2 yr
Tsang, 2001 9 20-30 100% at 5 yr
Yahalom, 2002 51 30 89% at 4 yr
Hitchcock, 2002 9 34 78% (100% local)
Chemotherapy for MALT
ORR CR Reference
Single Agent
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
Response to antibiotics
Reference n staging CR rate time to CR relapses procedure (%) (mos.) (n)
Savio, 1996 12 CT84 2-4 0
Pinotti, 1997 45 CT 67 3-18 2
Neubauer, 1997 50 CT±EUS 80 1-9 5
Nobre Leitao, 1998 17 CT+EUS 100 1-12 1
Steinbach, 1999 23 CT±EUS 56 3-45 0
Montalban, 2001 19 CT±EUS 95 2-19 0
Ruskone-Formestraux, 2001 24 CT+EUS 79 2-18 2
LY03 interim analysis, 2000 190 CT 62 3-24 15
Predictive factors for lack of response to antibiotics
• Deep infiltration of gastric wall
• Lymph node involvement
• Increased number of large cells
• t(11;18)
ESMO guidelines: localised stage
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
ESMO guidelines: advanced stage
IELSG 19 study
IELSG 19 study
Zucca et al, J Clin Oncol, 2013
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’
Histological transformation in MZL
Conconi et al, Annals Oncol, 2015
• 1995-2012• 340 patients with MZL• HT Bx-proven• Median follow-up: 5 yrs• 2-yr OS postHT: 57%
At 5 yrs:5%
Non-gastric MALT
Non-gastric MALT
Chlamydia psittaciv
Borrelia burgdorferi
Hashimoto thyroiditis
Sjögrensyndrome
Non-gastric MALT: outcome according to primary site
Zucca et al, Blood, 2003
MALT of the salivary glands: IELSG 41
Jackson et al, The Oncol, 2015
• 247 patients with MALT• 1983-2012• Median follow-up: 55 months
OAL and Chlamydia: IELSG 27
Ferreri et al, J Clin Oncol, 2012
48% eradication
RR: 65%
Summary
• Antigen-driven processes treatment ofinitiating event
• Disseminated disease, limited to mucosalsites, not associated with poor outcome
• Excellent prognosis (OS) regardless oftreatment
Thank you!