Optimal timeframes & summary

Evidence-based guidelines, where they exist, should inform timeframes. Treatment teams need to recognise that shorter timeframes for appropriate consultations and treatment can promote a better experience for patients. Three steps in the pathway specify timeframes for care (Figure 3). They are designed to help patients understand the timeframes in which they can expect to be assessed and treated, and to help health services plan care delivery in accordance with expert-informed time parameters to meet the expectation of patients. These timeframes are based on expert advice from the Low-Grade Lymphomas Working Group.

Timeframes for care

Step in pathway	Care point	Timeframe
Presentation, initial investigations and referral	Signs and symptoms	Presenting symptoms should be promptly and clinically triaged with a health professional.
	Initial investigations initiated by GP	For patients who do not need a prompt referral, all investigations should be completed, and a path of action decided, within 4 weeks of first presentation.
	Referral to specialist	Patients should be referred to a specialist: within 72 hours if the presence of lymphoma is highly likely within 4 weeks if listed indicators of concern are absent.
Diagnosis, staging and treatment planning	Diagnosis and staging	Timing of diagnostic investigations should be guided by the initial severity of symptoms. Staging should be completed within 4 weeks.
Diagnosis, staging and treatment planning	Multidisciplinary team meeting and treatment planning	A multidisciplinary team discussion is necessary and should be conducted before implementing treatment.
Treatment	Watchful waiting	Watchful waiting may be recommended for asymptomatic advanced stage MZL. Watchful waiting may also be recommended for stage II FL that is not amendable to radiation therapy and advanced stage FL (stages III and IV) based on symptoms and disease bulk. Also recommended for indolent subtype of MCL.
	Radiation therapy	Radiation should be considered in limited stage FL, in specific extranodal organ involvement (e.g. MZL of stomach, orbit) and for symptom control. Where appropriate, radiation therapy should begin within 4 weeks.
	Systemic therapy	In FL and MZL, the decision of when to start systemic therapy is guided by the presence of symptoms and organ dysfunction. Most MCL patients should begin treatment with systemic therapy within 2 weeks of completing staging.

Seven steps of the optimal care pathway

Step 1: Prevention and early detection

Step 2: Presentation, initial investigations and referral step

Step 3: Diagnosis, staging and treatment planning

Step 4: Treatment

Step 5: Care after initial treatment and recovery

Step 6: Managing refractory, relapsed, residual or progressive disease

Step 7: End-of-life care

Scope of the optimal care pathway for people with low-grade lymphomas Low-grade lymphomas are a heterogenous group of generally slow-growing non-Hodgkin B-cell lymphomas (NHL), which represent about 40 per cent of all NHL.

This optimal care pathway will cover follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). With respect to other low-grade lymphoma subtypes, small

lymphocytic lymphoma is being addressed as part of the chronic lymphocytic leukaemia optimal care pathway, while Waldenström’s macroglobulinaemia and hairy cell leukaemia may be addressed in a future optimal care pathway, noting that many of the principles outlined in this document are relevant to these lymphomas.

Follicular lymphoma – World Health Organization grades 1–3A

FL is the second most common subtype of NHL. FL makes up 20–30 per cent of all NHL and can progress to become diffuse large B-cell lymphoma in approximately 10 per cent of patients during their disease course.

Marginal zone lymphoma

MZL accounts for approximately 8 per cent of all NHL.

The three main types of MZL are distinct clinical entities with specific diagnostic criteria and different genetic features, clinical behaviour and therapeutic implications (ESMO 2020):

extranodal or mucosa-associated lymphoid tissue (MALT) lymphoma (this is the most common form of MZL, accounting for around two-thirds of all MZL)
splenic MZL (SMZL) accounts for around 20 per cent of all MZL
nodal MZL (NMZL) accounts for about 10 per cent of all

Mantle cell lymphoma

MCL is a rare subtype of low-grade lymphoma and may behave either as an aggressive disease or more slowly.

Low-grade lymphomas are traditionally perceived as ‘incurable’ lymphomas. However, many patients survive for more than 20 years and, given low-grade lymphomas are commonly diagnosed late in life, it may not significantly impact on their pre-morbid survival expectations.

Patients diagnosed with low-grade lymphomas will, in most cases, enter into lifelong follow-up, may have periods during which their lymphoma is monitored and not treated, and may need multiple different treatments for their lymphoma over their lifetime. While for many the truly slow-growing nature of the disease may mean patients die from other causes, in some patients the cause of death will be due to their lymphoma, and in a minority due to an aggressive change in their disease behaviour, called histologic transformation.

Noting the often-long trajectory that patients travel with their disease, this optimal care pathway focuses on pathways that enable the patient and their clinician to finesse a personalised approach that balances depth and duration of remission with treatment toxicity, optimising both duration and quality of life.