Systemic therapy is appropriate in most patients with non-contiguous stage II or stage III–IV disease who are symptomatic by GELF/BCNI criteria, and considered fit enough to experience a positive risk-benefit balance of undergoing treatment (Ardeshna et al. 2003; Brice et al. 1997). The choice of initial systemic therapy needs to consider the potential for sequencing of subsequent therapies, including potential future stem cell mobilisation.

Follicular lymphoma

Initial treatment with chemotherapy and anti-CD20 monoclonal antibody is often followed by continued therapy with anti-CD20 antibody maintenance for another two years. Given that ongoing maintenance antibody therapy increases progression-free survival but does not prolong overall survival, it is important the patient understands both the benefits in prolonging remission as well as the additional infectious toxicities of using maintenance antibody therapy.

Nodal marginal zone lymphoma

Initial treatment with chemotherapy and anti-CD20 monoclonal antibody is recommended.

Extranodal marginal zone lymphoma

Helicobacter pylori eradication therapy should be given to all patients with gastric MALT, irrespective of stage and Helicobacter pylori status. In those who remain Helicobacter pylori positive, second- line eradication therapy is recommended. Regression of lymphoma following successful eradication of Helicobacter pylori may be delayed, and so it is appropriate to wait 12 months before starting another treatment.

In other instances of localised MALT (e.g. conjunctival MALT), a trial of systemic therapy with antibiotics may be appropriate before radiation therapy.

MALT can also be treated with chemotherapy and anti-CD20 monoclonal antibody.

Splenic marginal zone lymphoma

Recognised first-line therapeutic options are rituximab monotherapy, splenectomy (after appropriate vaccinations) or chemotherapy and anti-CD20 monoclonal antibody combinations. While half of splenectomised patients do not need further treatment for SMZL, splenectomy may bring about complications and is increasingly being replaced with rituximab +/- chemotherapy as initial therapy, especially in patients with a heavy bone marrow disease burden.

Mantle cell lymphoma

MCL causing symptoms should be treated with systemic chemotherapy and anti-CD20 monoclonal antibody combination, incorporating high-dose cytarabine in younger, fitter patients, followed by consolidation with autologous stem cell transplantation (ASCT). Rituximab maintenance after ASCT has been shown to improve overall survival.

In older, more frail patients, chemotherapy and anti-CD20 monoclonal antibody combinations is appropriate. Where bendamustine-containing regimens are used, meticulous monitoring for infections is necessary.

Timeframes for starting treatment

The decision to start treatment may occur after a long period of watch and wait. In FL and MZL, the decision of when to start systemic therapy is guided by the presence of symptoms and organ dysfunction according to the GELF/BCNI criteria. Once the patient meets the criteria to start, treatment should begin within four weeks. Most symptomatic MCL patients should begin treatment with systemic therapy within two weeks of completing staging.

Training and experience required of the appropriate specialists

The following training and experience is required of the appropriate specialist(s): Haematologists and medical oncologists must have training and experience of this standard:

• Fellow of the Royal Australian College of Physicians (or equivalent)
• adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).

Cancer nurses should have accredited training in these areas:

• anti-cancer treatment administration
• specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
• the handling and disposal of cytotoxic waste (ACSQHC 2020).

Systemic therapy should be prepared by a pharmacist whose background includes this experience:

• adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or

If no haematologists or medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in line with a detailed treatment plan or agreed protocol, and with communication as agreed with the haematologists or medical oncologist or as clinically required.

Health service characteristics

To provide safe and quality care for patients having systemic therapy, health services should have these features:

• a clearly defined path to emergency care and advice after hours
• access to basic haematology and biochemistry testing
• cytotoxic drugs prepared in a pharmacy with appropriate facilities
• occupational health and safety guidelines for handling cytotoxic drugs, including safe prescribing, preparation, dispensing, supplying, administering, storing, manufacturing, compounding and monitoring the effects of medicines (ACSQHC 2011)
• guidelines and protocols for delivering treatment safely (including dealing with extravasation of drugs)
• coordination for combined therapy with radiation therapy, especially where facilities are not co-located
• timely access to pathology and blood