STEP 4: Treatment
Step 4 describes the optimal treatments for MDS, the training and experience required of the treating clinicians and the health service characteristics required for optimal cancer care.
All health services must have clinical governance systems that meet the following integral requirements:
- identifying safety and quality measures
- monitoring and reporting on performance and outcomes
- identifying areas for improvement in safety and quality (ACSQHC 2020).
Step 4 outlines the treatment options for MDS. For detailed clinical information on treatment options refer to the National Comprehensive Cancer Network MDS guideline.
The intent of treatment can be defined as one of the following:
- curative
- anti-cancer therapy to improve quality of life and/or longevity without expectation of cure
- supportive therapies to improve quality of life and/or longevity
- palliation
The treatment intent should be established in a multidisciplinary setting, documented in the patient’s medical record and conveyed to the patient and carer as appropriate.
The potential benefits need to be balanced against the morbidity and risks of treatment.
The lead clinician should discuss the advantages and disadvantages of each treatment and associated potential side effects with the patient and their carer or family before treatment consent is obtained and begins so the patient can make an informed decision. Supportive care services should also be considered during this decision-making process. Patients should be asked about their use of (current or intended) complementary therapies (see Appendix D).
Timeframes for starting treatment should be informed by evidence-based guidelines where they exist. The treatment team should recognise that shorter timeframes for appropriate consultations and treatment can promote a better experience for patients.
Initiate advance care planning discussions with patients before treatment begins (this could include appointing a substitute decision-maker and completing an advance care directive). Formally involving a palliative care team/service may benefit any patient, so it is important to know and respect each person’s preference (Australian Government Department of Health 2021a).
Treatment options for MDS patients will depend on patient factors (age, comorbidities, patient wishes) as well as disease factors (risk scores, cytopenias, symptoms).
All patients will receive best practice medical supportive care including education, active surveillance and monitoring, transfusions as appropriate and prompt infection control. There may be some lower risk MDS patients who are not on any active interventions who may be suitable for monitoring and surveillance with their general practitioner.
The range of disease-specific/directed additional treatment options varies across different risk groups depending on age and comorbidities. Options include:
- supportive interventions such as GCSF or EPO in some patients
- transfusion support
- chemotherapy – low dose or more intensive
- haemopoietic stem cell transplant
- clinical trials
- other specific agents depending on the patient’s clinical presentation or karyotype
The funding status of various treatment approaches is dynamic. Prescribers should ensure familiarity with eligibility criteria and discuss any financial implications of all treatment recommendations with patients before starting treatment.
Supportive therapies are required in all MDS patients and may be the only long-term treatment required for those with lower risk disease, or for older or unfit patients and those who have not responded to other treatments (Fenaux et al. 2021).
Supportive therapy may include the following:
- Conduct regular blood tests and review appointments with the patient’s general practitioner and specialist to monitor progress and symptoms.
- Manage anaemia, including red blood cell transfusions – frequency will be determined by symptoms and comorbidities.
- Manage bleeding, which may include platelet transfusions or tranexamic acid when
- Manage infections – prompt antibiotics for infection and consideration of short-term use of growth factors (e.g. GCSF). Infectious disease consultation may be required if infections recur. Anti-fungal prophylaxis may be considered in patients with persistent severe neutropenia depending on local guidelines and practice.
- Consider iron chelation therapy for transfusional iron overload. In general, this is considered for patients with significant transfusion burden and evidence for iron overload. Both oral and
Parenteral chelation therapy options are available and could be tailored to the patient depending on clinical need.
- Manage gastrointestinal symptoms such as nausea, vomiting, loss of appetite, dysgeusia, diarrhoea or constipation as a result of treatment. This requires optimal symptom control with medicine, nutritional advice, analgesia and mouth care (referral to a dietitian may be required if dietary intake is affected).
Timeframe for starting treatment
The timeframe for starting treatment should be guided by clinical presentation and urgency and disease progression over time.
Training and experience required of the physician
Documented evidence of the physician’s training and experience, including their specific (sub-specialty) experience with MDS and procedures to be undertaken, should be available.
Health service characteristics
To provide safe and quality care for patients, health services should have these features:
- medical staff availability
- diagnostic imaging
In patients with lower risk MDS, anaemia is the most common cytopenia. Erythropoiesis-stimulating agents may be used as first-line therapy.
Available treatment options include (Stojkov et al. 2020; Volpe & Komoroji 2021):
- lenalidomide – specifically approved for patients with transfusion-dependent lower risk MDS with del(5q) abnormality in their karyotype analysis
- hypomethylating agents (HMAs) including azacitidine in patients who progress to higher risk MDS
- immunosuppressive therapy to provide some haematological response among selected subsets of patients.
Timeframe for starting treatment
The timeframe for starting treatment should be guided by clinical presentation and urgency.
Training and experience required of the physician
Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in haematology.
Health service characteristics
To provide safe and quality care for patients having treatments, health services should have these features:
- critical care support
- 24-hour medical staff availability
- 24-hour high dependence or intensive care unit
- diagnostic imaging
- pathology diagnostics
- ready access to blood banking and transfusion
Survival for these patients is generally poor, so if appropriate for the disease, directed therapy treatment should be initiated promptly.
Standard therapies include (Bewersdorf et al. 2020; Sekeres & Cutler 2014) the following:
- hypomethylating agents (HMAs azacitidine and decitabine). Azacitidine has shown a survival benefit in patients with higher risk MDS and is the mainstay of therapy, with clinical benefit and haematological responses seen even in those who don’t achieve a complete remission. Treatment is usually continued for at least 6 months and continued based on response, though dose reductions or delays may be required in some patients.
- AML induction This can be considered in those with a high blast count and who are eligible for intensive therapy.
- Haematopoietic stem cell transplantation close to the time of diagnosis, depending on the patient’s goals of Consider proceeding to transplantation soon after an optimal donor is located.
- In the interim period before transplantation, HMA therapy, AML induction chemotherapy or enrolment in a clinical trial should be considered to prevent disease progression, although the optimal pre-transplantation therapy is unknown.
Timeframe for starting treatment
For symptomatic patients with higher risk disease, a decision about disease-specific therapy should be made and treatment begun within the first six weeks of initial specialist consultation. At times, depending on disease stability and symptoms, ongoing close monitoring could be considered depending on the patient’s circumstances.
Training and experience required of the physician
Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in haematology.
To oversee higher risk MDS patient care, the physician should have worked or be working in a team with experience in managing MDS and AML, and specifically the use of HMAs or intensive chemotherapy.
Documented evidence of the physician training and experience, including their specific (sub-specialty) experience with MDS and procedures to be undertaken, should be available.
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 adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.
In a setting where no haematologist 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 accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.
Health service characteristics
To provide safe and quality care for patients having systemic therapy for higher risk MDS, health services should have these features:
- critical care support
- 24-hour medical staff availability
- 24-hour high dependence or intensive care unit
- diagnostic imaging
- pathology diagnostics
- ready access to blood banking and transfusion
Allogeneic stem cell transplantation is the only potentially curative treatment of MDS (Bewersdorf et al. 2020; Skeres & Cutler 2014). In this procedure, the patient receives blood-forming cells (stem cells) from a healthy donor (related or unrelated) to replace their own stem cells following chemotherapy and, in some cases, radiation.
Patients may have additional supportive care requirements to address the immunosuppressive effects and long-term side effects of stem cell transplantation. Issues may include infertility, GVHD, increased risk of infection, iron overload or anaemia, bleeding, mouth ulcers and fatigue.
Timeframe for starting treatment
A referral to a bone marrow transplant specialist should occur once transplantation is considered a potential treatment option for a patient with higher risk MDS and occasionally lower risk MDS.
Early referral to a transplant specialist is recommended for patients under 70 years of age and with higher risk MDS. Age-specific frailty scores and performance status should be considered for such a referral rather than an absolute age cut-off.
Training and experience required of the physician
Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in bone marrow transplantation.
Documented evidence of the physician’s training and experience, including their specific (sub- specialty) experience with MDS and procedures to be undertaken, should be available.
Health service characteristics
To provide safe and quality care for patients having haematopoietic stem cell transplant, health services should have these features:
- critical care support
- 24-hour medical staff availability including access to consultative medical subspeciality services
- 24-hour operating room access, high dependency unit and intensive care unit
- bone marrow transplantation unit with ancillary medical and allied health support
- diagnostic imaging
- pathology diagnostics
- ready access to blood banking and transfusion
Combinations of hypomethylating agents (HMAs, especially with immune checkpoint inhibitors, have shown promising signals in both the frontline and HMA-refractory setting.
Several other novel agents including orally available and longer acting HMAs, the BCL-2 inhibitor venetoclax, oral agents targeting driver mutations (IDH1 and IDH2, FLT3), immunotherapies and new options for intensive chemotherapy are being studied in clinical trials (Bewersdorf et al. 2020). Examples of non-chemotherapy approaches include therapy targeting marrow microenvironment and immune checkpoints such as TIM-3 and antiCD47 monoclonal antibody-magrolimab.
Examples of new treatments for adults with MDS, approved by the America’s Food and Drug Administration, include luspatercept (Reblozyl) for lower risk MDS and the oral combination of decitabine and cedazuridine (Inqovi) for higher risk MDS (Harris 2020).
Clinical trials for MDS may be available, especially in those with higher risk disease, and they may also be eligible for AML trials. Refer to section 4.4 for clinical trial resources.
The key principle for precision medicine is prompt and clinically oriented communication and coordination with an accredited laboratory and pathologist. Tissue analysis is integral for access to emerging therapies and, as such, tissue specimens should be treated carefully to enable additional histopathological or molecular diagnostic tests in certain scenarios.
Palliative care is a multidisciplinary approach to symptom management, psychosocial support and assistance in identifying care goals for patients with serious illness and their families.
Early referral to palliative care can improve the quality of life for people with cancer and in some cases may be associated with survival benefits (Haines 2011; Temel et al. 2010; Zimmermann et al. 2014). This is particularly true for cancers with poor prognosis.
The lead clinician should ensure patients receive timely and appropriate referral to palliative care services. Referral should be based on need rather than prognosis. Emphasise the value of palliative care in improving symptom management and quality of life to patients and their carers.
The ‘Dying to Talk’ resource may help health professionals when initiating discussions with patients about future care needs (see ‘More information’). Ensure that carers and families receive information, support and guidance about their role in palliative care (Palliative Care Australia 2018).
Patients, with support from their family or carer and treating team, should be encouraged to consider appointing a substitute decision-maker and to complete an advance care directive.
Refer to step 6 for a more detailed description of managing patients with relapsed or progressive disease.
More information
These online resources are useful:
- The team should support the patient to participate in research or clinical trials where available and appropriate. Many emerging treatments are only available on clinical trials that may require referral to certain trial centres.
For more information visit:
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, neuropathy, sleep changes, 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 bruising or bleeding and recurrent infections
- decline in mobility or functional status as a result of disease progression
- 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’s 13 11 20 and the Leukaemia Foundation’s 1800 620 420 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
More information
Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.