Introduction: Indolent lymphomas are neoplasms of the mature B-cell that have the survival measure in years even without direct treatment. This group contains follicular lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphoma. Mantle cell lymphoma, although can have an indolent course, it's not included here.

Follicular lymphoma (FL): FL is the second in prevalence between non-Hodgkin's lymphomas (NHL) and the most common with an indolent presentation.1 Patients can have a heterogeneous evolution, from asymptomatic disease without need for therapy until an aggressive course with poor chemotherapy response. The latter tends to belong in a group of progressive disease within two years of first therapy (POD24).2 Although a better knowledge of the disease biology, there are current no clear prognostic system that can separate patients in need for aggressive treatment versus those with no need for treatment at all. But it is considered standard only treat patients with high tumor burden or symptomatic. Generally, patients that do need therapy receive CHOP/CVP or Bendamustine with additional anti-CD20 antibody. There seems to be a favorable group that can be treated with Rituximab monotherapy and remain without need for new treatment for a long period.3 After the GALLIUM trial,4 where Obinutuzumab was associated with 34% reduction in progression versus Rituximab, this novel anti-CD20 antibody became an option. Although a progression-free survival (PFS) benefit was demonstrated, there was no gain in overall survival (OS) at this point. Maintenance with Rituximab or Obinutuzumab is generally recommended (every 2 months for 2 years), with long term follow up from the PRIMA trial showing a sustained difference in PFS.5 However, no OS superiority was observed. To reduce toxicity while maintaining efficacy, Lenalidomide plus Rituximab regimen was tested in untreated FL patients (“R2”).6 This “chemo-free” protocol had an equal PFS rate at 3 years compared with Rituximab plus Chemotherapy, with less hematological toxicity and neutropenic fever. The combination was also effective in the relapse setting, with a median of 40 months in PFS.7 Chimeric antigen receptor-modified T cells (CAR-T) against CD19 is becoming widely use in lymphoma and has showed efficacy in relapse/refractory FL patients, with report of high complete remission rate and sustained remissions.8

Lymphoplasmacytic lymphoma (LPL): LPL is a lymphoma characterize by lymphoplasmacytic cells that produces monoclonal protein (IgM) and infiltrate the bone marrow and lymph nodes. When there is a measure IgM monoclonal production, LPL is a synonymous of Waldenström macroglobulinemia (WM). The MYD88 L265P mutation occurs in over 90% of cases,9 serving as a strong diagnostic marker (although not specific of WM). This mutation also has a prognostic role, with patients with the wild type showing a worse prognosis.10CXCR4 is another frequent and important mutation (prevalence of 30% in WM), that together with MYD88 can guide the treatment choice.11 WM is an incurable disease of normally elderly patients and the treatment, when needed, focus on achieving a response (rarely complete remission) while maintaining low toxicity.12 DRC is an option for low tumor burden and more frail patients that do not need urgent treatment. BDR serves well patients for patients with cytopenias and no neuropathy, while BR maybe prefer in bulky disease with high tumor burden.13 Ibrutinib with or without rituximab can be used in first line14 or relapsed patients,15 especially with the MYD88 mutation. Acalabrutinib and Venetoclax are other new options, with the last as one of the few active treatments in patient's refractory to ibrutinib.16

Marginal Zone B-cell lymphomas (MZL): The marginal zone B-cell lymphomas (MZLs) comprise extra nodal MZL (EMZL) of mucosa-associated lymphoid tissue (MALT), splenic MZL (SMZL) with or without villous lymphocytes and nodal MZL (NMZL) with or without monocytoid B cells. These are three distinct clinical entities with specific diagnostic criteria, clinical and therapeutic implications.17

Regarding to localize H. pylori-positive gastric MZL, the initial treatment should be H. pylori eradication. This treatment can induce lymphoma regression and long-term clinical disease control in the most of 50% of the patients.18 In patients who do not achieve lymphoma regression following antibiotic therapy, irradiation and systemic oncological therapies should be used, depending on the stage of disease. Patients who require systemic treatment, chemotherapy, immunotherapy or both are all effective.19 SMZL in asymptomatic patients, watch-and-wait is recommended and splenectomy is considered as the recommended first treatment. Rituximab therapy alone can be indicated and has an important response rate with minimal toxicity, particular useful in patients with autoimmune disorders.20 For asymptomatic patient diagnosed with NMZL is also recommended only observation. If systemic treatment is indicated, chemo-immunotherapy can be performed.21