Management of Extranodal Marginal Zone Lymphoma: Present and Upcoming Perspectives

Abstract

Extranodal marginal zone lymphoma (EMZL) encompasses a subgroup of non-Hodgkin lymphomas that often present with localized involvement and may manifest in a diversity of organs and tissues. EMZL pathogenesis is in some cases linked to chronic inflammation/infection, which may impose additional diagnostic and clinical challenges. The most studied and established connection is the presence of Helicobacter pylori in gastric EMZL. Due to its heterogeneity of presentation and intricate pathological features, treatment can be complex, and staging systems are decisive for the choice of therapy. Nevertheless, there is no consensus regarding the most suitable staging system, and recommendations vary among different countries. As a rule of thumb, in limited stages, a local therapy with surgery or radiation is the preferred option, and it is potentially curative. Of note, eradicating the causal agent may be an important step of treatment, especially in gastric EMZL, in which Helicobacter pylori eradication remains the first-line therapy for the majority of patients. In patients with more advanced stages, watch-and-wait is a valuable option, especially amongst those without clear indications for systemic therapy, and it may be carried on for several years. If watch-and-wait is not an option, systemic therapy may be needed. Even though several agents have been tested as monotherapy or in combination in recent years, there is no consensus regarding the first-line therapy, and decisions can vary depending on individual factors, such as age, clinical performance and stage. This review aims to discuss the several aspects of EMZL, including genetic milieu, pathogenesis and staging systems, that may influence the choice of therapy. In addition, we present a summary of evidence of several systemic therapies, compare different recommendations worldwide and discuss future perspectives and novelties in its therapy.

Time trends and survival of marginal zone lymphoma over 25 years in Girona, Spain (1994–2018)

“…These lymphomas are closely related to HP infection, 20 , 36 , 37 and the increase in the diagnosis and treatment of this infection has reduced the risk of this type of lymphoma. In our study, four out of five cases (78%) of gastric extranodal MZL showed this infection, similar to previous findings 38 , 39 ; in fact, its eradication is considered the main and most important step in the therapeutic strategy although certain cases with the genetic abnormality BIRC3::MALT1 do not respond to it. 39 , 40 …”

“…In our study, four out of five cases (78%) of gastric extranodal MZL showed this infection, similar to previous findings 38,39 ; in fact, its eradication is considered the main and most important step in the therapeutic strategy although certain cases with the genetic abnormality BIRC3::MALT1 do not respond to it. 39,40 MZL of the respiratory system, oral cavity and pharynx, eyes and adnexa were also found to be more common in men. Although there are not many population data to contrast with this result, both the study by Khalil et al, 3 and some case series on non-Hodgkin's lymphomas of the respiratory system and oropharynx show data consistent with ours.…”

“…In addition, a significant proportion was diagnosed at an early stage, and these cases were considered indolent, with low rates of proliferation and low risk of progression. 39 Regarding the 5-year survival of nodal MZL and SMZL, it is estimated at around 75% in our study. In the case of SMZL, the majority of patients were observed to present an indolent course of the disease, although around 30% showed a worse prognosis and some underwent transformation to diffuse large B-cell lymphoma.…”

“…This could, in part, be due to the eradication of the causal agent (HP) as first‐line treatment in gastric MALT cases attributable to this infection, which in turn are the most incident in this group. In addition, a significant proportion was diagnosed at an early stage, and these cases were considered indolent, with low rates of proliferation and low risk of progression 39 …”

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma

“…Radioimmunotherapy can be an alternative option for patients who cannot undergo systemic chemotherapy in the case of disseminated lymphoma. 11 Previous phase II studies have confirmed the efficacy and safety of 131 I-rituximab as salvage therapy in patients with relapsed or refractory B-cell NHL. [12][13][14] In addition, 90 Y-ibritumomab 2 Clinical Medicine Insights: Oncology tiuxetan ( 90 Y-ibritumomab tiuxetan; Zevalin; Biogen Idec Inc., San Diego, CA, USA; Schering AG, Berlin, Germany) has shown favorable efficacy outcomes in patients with MZL.…”