Treating asymptomatic early-stage CLL does not improve survival, so an initial ‘watch and wait’ approach is recommended.

Patients with early asymptomatic CLL (Rai 0–1) should be monitored every three months during the first year, and then every three to 12 months, depending on the stability and specific characteristics of their disease (Eichhorst et al. 2021). For those with asymptomatic Rai 0 or 1 disease, this can be with local blood tests and telehealth review if such processes align with the patient’s wishes.

Chemotherapy is not recommended for patients with TP53 mutation or del(17p) due to its poor efficacy in this setting. However, a number of patients may benefit from systemic therapy.

Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy has established curative potential for the subset of patients with favourable biologic features (IGVH mutated status and absence of TP53 dysfunction), and can be considered in younger, fit patients with adequate renal function (age < 65 with creatinine clearance ≥ 70 mL/min).

In patients with significant comorbidities or impaired organ function, less intensive chemoimmunotherapy such as chlorambucil and obinutuzumab or bendamustine and rituximab is also available. These treatments can be life-prolonging but do not have curative potential.

An allogeneic bone marrow transplant can be curative in patients with CLL but is rarely indicated. However, potentially suitable patients should be identified, and discussions with a linked transplantation service should begin early in the patient’s disease course.

Timeframes for starting treatment

Rate of disease progression is usually gradual and treatment initiation is rarely urgent. Timing should be discussed to align with the patient’s preferences but not delayed to the point where impaired performance status, compromised organ function or recurrent severe infections occur.

Training and experience required of the appropriate specialists

Haematologists/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 preparations, such as those provided by eviQ .

If no haematologist/medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner, general physician 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 primary managing specialist or as clinically required.

The training and experience of the appropriate specialist should be documented.

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 diagnostic pathology including basic haematology and biochemistry, and imaging
• access to appropriate molecular pathology access (not required on site and can be through central specialist laboratory)
• access to cytotoxic drugs prepared in a pharmacy with appropriate facilities
• occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019)
• guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
• coordination for combined therapy with radiation therapy, especially where facilities are not co-located.

Targeted therapies are the preferred treatment approach in all patients with TP53 mutation or del(17p) and can be considered in other patient subgroups:

• time-limited therapy with the combination of venetoclax plus obinutuzumab – for patients with a cumulative illness rating scale (Al-Sawaf et 2020) score of 6 or above or patients with impaired renal function
• continuous treatment with Bruton’s tyrosine kinase (BTK) inhibitors, including ibrutinib (Burger et al. 2015) and acalabrutinib (Sharman et al. 2020), until disease progression or intolerance.

The funding status of various treatment approaches is dynamic and prescribers should ensure familiarity with eligibility criteria and discuss any financial implications of all treatment recommendations with patients prior to treatment initiation.

There is no routine therapeutic role for surgery in managing patients with CLL, except for very rare instances where splenectomy can be beneficial (Cusack et al. 1997).

Radiation therapy can be used to treat obstructive/bulky nodes or massive symptomatic splenomegaly, or to reduce symptoms during palliative treatment (e.g. pain resulting from lytic bone lesions).

Timeframe for starting treatment

Where organ preservation is the goal (e.g. hydronephrosis) radiation should be commenced within 72 hours of recognition of the issue.

Where applied with symptomatic/palliative goals, appropriate timing is guided by the severity of the relevant symptoms but is rarely urgent and can be commenced within two weeks in most cases. This is due to the chronic nature of the underlying process.

Training and experience required of the appropriate specialists

There are no specific sub-specialty skill needs required for the delivery of palliative radiation in CLL beyond those generally required for registration and practice as a radiation oncologist.

The training and experience of the radiation oncologist should be documented.

Health service unit characteristics

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

• linear accelerator (LINAC) capable of image-guided radiotherapy (IGRT)
• dedicated CT planning
• access to MRI and PET imaging
• automatic record-verify of all radiation treatments delivered
• a treatment planning system
• medical physicists, radiation therapists and nurses with radiation therapy experience
• coordination for combined therapy with systemic therapy, especially where facilities are not co-located
• participation in Australian Clinical Dosimetry Service audits
• an incident management system linked with a quality management

Emerging therapies include:

• newer generation BTK inhibitors such as zanubrutinib (Tam et al. 2020) and pirtobrutinib (LOXO-305) (Mato et al. 2021)
• CAR T-cell therapy, a cellular therapy, directed against the CD19 surface molecule (Mancikova & Smida 2021)
• other emerging monoclonal

There are currently no approved therapies for CLL that specifically target acquired genomic mutations beyond TP53 dysfunction identifying a subgroup of patients where chemoimmunotherapy is contraindicated.

See validated screening tools mentioned in Principle 4 ‘Supportive care’.

A number of specific challenges and needs may arise for patients at this time:

• assistance for dealing with emotional and psychological issues, including body image concerns, fatigue, quitting smoking, traumatic experiences, existential anxiety, treatment phobias, anxiety/ depression, interpersonal problems and sexuality concerns
• potential isolation from normal support networks, particularly for rural patients who are staying away from home for treatment
• management of physical symptoms such as nausea, diarrhoea, fatigue or other specific treatment-related adverse events that will vary by agent
• decline in mobility or functional status as a result of treatment
• assistance with beginning or resuming regular exercise with referral to an exercise physiologist or physiotherapist (COSA 2018; Hayes et al. 2019).

Early involvement of general practitioners may lead to improved cancer survivorship care following acute treatment. General practitioners can address many supportive care needs through good communication and clear guidance from the specialist team (Emery 2014).

Patients, carers and families may have these additional issues and needs:

• financial issues related to loss of income (through reduced capacity to work or loss of work) and additional expenses as a result of illness or treatment
• advance care planning, which may involve appointing a substitute decision-maker and completing an advance care directive
• legal issues (completing a will, care of dependent children) or making an insurance, superannuation or social security claim on the basis of terminal illness or permanent disability.

Cancer Council 13 11 20, Leukaemia Foundation 1800 620 420 and Lymphoma Australia 1800 953 081 information and support lines can assist with information and referral to local support services.

A number of specific challenges and needs may arise for patients at this time: Consider:

• correction of vitamin D deficiency (Molica et 2012; Shanafelt et al. 2011)
• immunoglobulin replacement therapy for patients with hypogammaglobulinemia and frequent infections. The National Blood Authority has information on the eligibility criteria for immunoglobulins

For more information on supportive care and needs that may arise for different population groups, see Appendices A, B and C.

Rehabilitation may be required at any point of the care pathway. If it is required before treatment, it is referred to as prehabilitation (see section 3.6.1).

All members of the multidisciplinary team have an important role in promoting rehabilitation. Team members may include occupational therapists, speech pathologists, dietitians, social workers, psychologists, physiotherapists, exercise physiologists and rehabilitation specialists.

To maximise the safety and therapeutic effect of exercise for people with cancer, all team members should recommend that people with cancer work towards achieving, and then maintaining, recommended levels of exercise and physical activity as per relevant guidelines. Exercise should be prescribed and delivered under the direction of an accredited exercise physiologist or physiotherapist with experience in cancer care (Vardy et al. 2019). The focus of intervention from these health professionals is tailoring evidence-based exercise recommendations to the individual patient’s needs and abilities, with a focus on the patient transitioning to ongoing self-managed exercise.

Other issues that may need to be dealt with include managing cancer-related fatigue, improving physical endurance, achieving independence in daily tasks, optimising nutritional intake, returning to work and ongoing adjustment to cancer and its consequences. Referrals to dietitians, psychosocial support, return-to-work programs and community support organisations can help in managing these issues.

The lead or nominated clinician should take responsibility for these tasks:

• discussing treatment options with patients and carers, including the treatment intent and expected outcomes, and providing a written version of the plan and any referrals
• providing patients and carers with information about the possible side effects of treatment, managing symptoms between active treatments, how to access care, self-management strategies and emergency contacts
• encouraging patients to use question prompt lists and audio recordings, and to have a support person present to aid informed decision making
• initiating a discussion about advance care planning and involving carers or family if the patient

The general practitioner plays an important role in coordinating care for patients, including helping to manage side effects and other comorbidities, and offering support when patients have questions or worries. For most patients, simultaneous care provided by their general practitioner is very important.

The lead clinician, in discussion with the patient’s general practitioner, should consider these points:

• the general practitioner’s role in symptom management, supportive care and referral to local services
• using a chronic disease management plan and mental health care management plan
• how to ensure regular and timely two-way communication about:
  • the treatment plan, including intent and potential side effects
  • supportive and palliative care requirements
  • the patient’s prognosis and their understanding of this
  • enrolment in research or clinical trials
  • changes in treatment or medications
  • the presence of an advance care directive or appointment of a substitute decision-maker
  • recommendations from the multidisciplinary

More information

Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.