Management of marginal zone lymphomas-Updated ESMO guidelines

Marginal zone lymphomas represent approximately 5%–15% of all non-Hodgkin lymphomas in the Western world. EMZLs comprise approximately two-thirds and can arise at any extranodal site, usually in the context of chronic antigenic stimulation due either to infections or autoimmune disorders.

European Society for Medical Oncology (ESMO) has published updated guidelines on the management of marginal zone lymphomas (MZThis updated ESMO Clinical Practice Guideline provides key recommendations on the management of marginal zone lymphomas. It has been Authored by a multidisciplinary group of experts from different institutions and countries in Europe and abroad. A summary of recommendations is provided, including levels of evidence and grades of recommendation where applicable. The distinct disease entities (i.e. extranodal, nodal and splenic marginal zone lymphomas) are discussed separately. The organ-specific peculiarities are addressed in the recommendations for extranodal marginal zone lymphomas (MALT lymphomas).

Key recommendations include the following:

1. Staging and risk assessment

• Initial staging for all MZL subtypes should include history and physical examination, full blood and differential counts, biochemistry including renal and liver function tests, protein electrophoresis, LDH and B2M, serum and urine immunofixation, serology for HBV, HCV and HIV and cryoglobulins and cryocrit if HCV-positive
• IHC panel including at least CD20, CD10, CD5, CD23, cyclin D1 and IgD with diagnostic evaluation by an expert haematopathologist [IV, B]
• Clinical and biological prognosticators (HPLL, MALT-IPI) should be applied in clinical routine to estimate the clinical behaviour [III–IV, C]

2. Treatment

• EMZL
• Helicobacter pylori eradication therapy should be given to all patients with gastric MZL [II, A]
• ISRT is the preferred option for treatment of localised EMZL (moderate dose, which may vary according to the site) [II–IV, A–B]
• Anti-HCV therapy is recommended in patients with HCV-associated lymphoma [IV, B]
• Other treatments including ChT, immunotherapy or combination chemoimmunotherapy are indicated in patients with symptomatic disseminated disease, contraindications to RT, failure after antibiotics or after local therapy or clinical suspicion of histological transformation: R-chlorambucil [I, A], R-bendamustine [III, A], rituximab monotherapy [III, B], R-lenalidomide [III, C] and R-CHOP for (clinically suspected or biopsy-proven) histological transformation
• SMZL
• Rituximab alone is the preferred initial therapy in patients with SMZL [III, A]
• Chemoimmunotherapy is indicated when rituximab alone is ineffective or in the presence of disseminated symptomatic disease and/or signs of high-grade transformation [III, B]
• Anti-HCV therapy should be considered in patients with HCV-associated lymphoma [IV, B]
• Splenectomy may be considered in selected cases, when rituximab is not indicated or ineffective [IV, B]
• NMZL
• Treatment should follow the principles of therapy for follicular lymphoma [IV, B]
• Anti-HCV therapy should be considered in patients with HCV-associated lymphoma [IV, B]
• Chemoimmunotherapy is recommended in patients with NMZL (e.g. R-bendamustine, R-CHOP, R-CVP) [IV, B]

3. Response evaluation and follow-up

• Asymptomatic patients with disseminated MZL (SMZL and NMZL) being managed by watch-and-wait should be monitored by physical examination, imaging as clinically required, blood counts and biochemistry every 6 months
• Patients with EMZL at non-gastric sites can be re-evaluated with clinical examination, laboratory work-up and imaging/biopsy of residual lesions if indicated every 3 months for the first 2 years, and every 6 months thereafter
• Gastric MZL
• Sequential evaluation of gastric biopsies remains an essential follow-up procedure for gastric MZL, particularly in patients with persistent Helicobacter pylori infection
• SMZL
• Specific criteria for response assessment are recommended for SMZL and achievement of CR is defined by normal spleen size, normal blood counts, negative flow cytometry on blood and negative IHC on bone marrow biopsy

Follow-up

Asymptomatic patients with disseminated MZL (SMZL and NMZL) on watch-and-wait should be assessed every six months

EMZL at non-gastric sites, follow-up every three months for the first two years, and every six months thereafter.

For further reference log on to:

Zucca E, Arcaini L, Buske C, Johnson PW, Ponzoni M, Raderer M, et al. European Society for Medical Oncology. Marginal Zone Lymphomas: ESMO Clinical Practice Guidelines. Ann Oncol 2020;31(1):17-29. Doi: 10.1016/j.annonc.2019.10.010. PMID: 31912792.