4.2 Treatment options

4.2 Treatment options

Disease-directed therapy should not be initiated unless there are disease-related symptoms or evidence of disease progression. According to the iwmm guidelines (Hallek et al. 2018), signs of ‘active disease’ include any of the following:

  • new or worsening anaemia or thrombocytopenia
  • massive, progressive or symptomatic splenomegaly or lymphadenopathy
  • sustained progressive lymphocytosis (50 per cent or greater increase over two months or lymphocyte doubling time in under six months)
  • autoimmune complications including anaemia or thrombocytopenia that respond poorly to corticosteroids
  • extranodal involvement impacting organ function or causing symptoms (e.g. skin, kidney, lung, spine)
  • any of these disease-related symptoms: unintentional weight loss of more than 10 per cent within the last six months; extreme fatigue (unable to work or perform usual activities), fever of 38°C

for two or more weeks without evidence of infection; night sweats for a month or longer without evidence of infection.

For more detailed information on the criteria for initiating treatment, see the iwmm guidelines 

Treatment decisions will be based on TP53 mutation or del(17p), IGHV mutational status, age, comorbidities, potential interactions with other medicines and patient preference (Eichhorst et al. 2021).

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:

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