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!