Virtually all patients treated for MM will receive systemic therapy.

Induction therapy is the first phase of initial therapy. It aims to rapidly reduce the burden of MM. Induction therapy can include a combination of:

• immunomodulatory drugs (IMiDs)
• proteasome inhibitors (PIs)
• chemotherapy
• monoclonal antibodies (mAbs)

Induction regimens will differ depending on whether the patient is eligible for a transplant and/ or fit for high-dose chemotherapy. Typically, transplant-eligible patients will undergo a three-drug

combination induction therapy that contains an IMiD and a PI with corticosteroids. Patients who are not transplant eligible may undergo the same triple combination with dose attenuation, or a double combination containing an IMiD or a PI with corticosteroids. Factors such as potential toxicity and patient fitness should be considered when choosing a combination.

Autologous stem cell transplant

ASCT uses the patient’s own stem cells to facilitate a faster bone marrow recovery after high-dose chemotherapy. When incorporated into initial treatment, ASCT improves both progression-free survival and overall survival compared with a non-ASCT approach for transplant-eligible patients.

It is recommended for patients up to age 70 who have good performance status and organ reserve.

Tandem ASCT

Patients with high-risk cytogenetics may benefit from a second ASCT within six months of the first. This option has higher acute toxicity.

Allogeneic stem cell transplant

AlloSCT uses stem cells from a donor rather than the patient’s own stem cells. Due to the lack of consistent survival benefit, alloSCT is not standard of care. However, for patients with high-risk MM who have a poor long-term prognosis, it may be considered in their initial course of therapy or first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant- related risks. It is recommended that alloSCT be performed in a clinical trial setting.

Consolidation therapy

This is a short course of drug therapy of similar intensity to induction therapy that is given after ASCT to further reduce the burden of myeloma. Consolidation therapy is not routine but may benefit some patients who have not had effective induction therapy and who have not achieved complete remission post ASCT.

Maintenance therapy

This is continuous drug treatment to keep the MM in remission and is usually given for at least two years or until disease progression.

For more information see the MSAG Clinical practice guideline: multiple myeloma (Quach & Prince 2019).

Timeframes for starting treatment

Treatment should begin within two weeks of establishing the diagnosis and staging. However, in cases with critical organ compromise, such as renal failure and cord compression, or rapid clinical progression, it may be vital to start treatment within 24 hours of diagnosis.

Training and experience required of the appropriate specialists

Haematologists or 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).

Myeloma specialist nurses are recommended where possible, as specialist cancer nurses have been shown to improve symptom control, treatment adherence, self-efficacy and patient-reported outcomes, as well as reducing unplanned hospital admissions (Charalambous et al. 2018).

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 preparation.

In cases where no haematologist is locally available (e.g. regional or remote areas), some components of less complex therapies, such as bisphosphonate therapy or other supportive 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 accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist 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
• 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
• appropriate molecular pathology

Hospital or treatment unit characteristics for providing safe and quality care for ASCT include:

• access to National Association of Testing Authorities (NATA)-accredited apheresis for collecting peripheral blood progenitor cells, with appropriately credentialed nursing staff available to operate cell separators
• access to a NATA-accredited therapeutic cellular laboratory for the appropriate cryopreservation and handling of peripheral blood progenitor cells
• dedicated credentialed transplant haematologists and a multidisciplinary team credentialed in caring for high-acuity patients
• access to an onsite intensive care unit with credentialed intensivists
• dedicated standard isolation rooms (single rooms with ensuite and clinical hand-washing facilities).

A number of patients may benefit from radiation therapy. Radiation therapy can provide rapid local control of MM or plasmacytoma that is causing pain or acute organ compromise such as spinal cord compression.

In patients with solitary bone plasmacytoma or solitary extramedullary plasmacytoma, radiotherapy alone can offer durable control, and potentially cure.

Timeframe for starting treatment

• For acute critical organ compromise, such as symptomatic spinal cord compression, patients should start radiotherapy within 24 hours of referral where possible, with a maximum acceptable waiting time within 48 hours.
• For symptomatic tumours causing pain, radiotherapy should begin within 48 hours of referral where possible, with a maximum acceptable waiting time of 14 days.
• For solitary bone plasmacytoma or extramedullary plasmacytoma where the treatment goal is curative, radiotherapy should begin within 14 days of referral where possible, with a maximum acceptable waiting time of 28 days.
• These timeframes concur with the Royal Australian and New Zealand College of Radiologists guidelines (RANZCR 2013).

Training and experience required of the appropriate specialists

Fellow of the Royal Australian and New Zealand College of Radiologists or equivalent, with adequate training and experience, institutional credentialing and agreed scope of practice in MM.

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
• trained 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

There is no routine therapeutic role for surgery in managing patients with MM except for preventing or stabilising long-bone pathological fractures and vertebral column instability, as well as cases of spinal cord compression that are not treatable by radiotherapy (Terpos et al. 2021).

Supportive therapies are important in the management of MM and should be offered where indicated concurrently with anti-myeloma therapies from the beginning of treatment. The following should be considered:

• bisphosphonate therapy for all patients requiring MM treatment unless contraindicated, with calcium and vitamin D supplements where indicated for bone strengthening
• venous thromboembolism (VTE) prophylaxis is recommended for patients who are treated with IMiDs (e.g. thalidomide, lenalidomide or pomalidomide)
• recombinant erythropoietin (rEpo) may be considered in selected patients with transfusion dependent anaemia, especially in those with renal failure
• infection prophylaxis should be considered where indicated, including:

• immunoglobulin replacement therapy for patients with frequent infections – see the National Blood Authority website for criteria for the clinical use of intravenous immunoglobulin in Australia
• pharmaceutical prophylaxis including that against varicella zoster reactivation and

Pneumocystis jiroveci should follow institutional guidelines

• vaccinations against hepatitis B, pneumococcus, influenza and other pathogens that are deemed necessary because of epidemiologic prevalence (live vaccines should be avoided)
  • for symptomatic localised bone lesions:
• localised radiation may be beneficial in patients with bone pain who have a well-defined focal process
• patients with lytic lesions threatening long-bone fractures should be referred to orthopaedics for consideration of prophylactic internal fixation
• patients with spinal compression fractures and disabling pain may benefit from balloon kyphoplasty; the benefit of vertebroplasty is unclear.

For MM-specific supportive care, please refer to the MSAG Clinical practice guideline: multiple myeloma (Quach & Prince 2019).

A range of biological, targeted and novel immunotherapeutic approaches are being used to treat MM. Some of these agents may not be reimbursed on the Australian Pharmaceutical Benefits Scheme (PBS) but may be available through clinical trials. Efforts should be made to identify patients who may be eligible for clinical trials, particularly when PBS options are exhausted.

Some emerging therapies include:

• chimeric antigen receptor T-cells
• bispecific antibodies (T-cells engagers or natural killer cell engagers)
• antibody-drug conjugates
• novel monoclonal antibodies
• cereblon E3 ligase modulators
• BCL2 inhibitors (these are particularly effective for patients with the cytogenetic lesion of t(11;14)
• selective inhibitor of nuclear

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 pain, fatigue and symptoms related to side effects of treatment
• 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).

For MM-specific supportive therapies, please refer to step 4.2.4.

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’s 13 11 20 information and support line can assist with information and referral to local support services.

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