Guidelines on the Diagnosis and Management of Multiple Myeloma

4. General Measures and Supportive Care

Optimal general management is fundamental and should be a key part of the overall care plan. Despite the importance of supportive care, there is little published research and the majority of the following recommendations are Grade C based on Level IV evidence. Patients should be informed appropriately about the condition, its potential complications and the importance of supportive measures. These are summarised in Table III. Despite the importance of supportive care, there is little published research and the majority of the recommendations in Table III are Grade C based on Level IV evidence.

Table III: General Aspects of Care in Myeloma

Hydration; renal function	Maintain adequate hydration (fluid intake of at least 3 l/day)in all patients. Avoid potentially nephrotoxic drugs when possible.
Hypercalcaemia	Volume replacement with intravenous saline and an intravenous bisphosphonate. (A loop diuretic is not of additional benefit unless there is volume overload).
Bone disease & pain management: There should be an active approach to pain control; it can be helpful to enlist the support of palliative care teams in obtaining pain control for myeloma patients.	Analgesia: A variety of analgesics may be used, including simple analgesics, opiates and fentanyl patches. NSAIDs should be avoided in patients with renal impairment and used with caution in other patients. Chemotherapy and radiotherapy: Response to chemotherapy is a major factor in reducing progression of bone disease. Local radiotherapy may be of benefit in patients with localised severe pain. Orthopaedic surgery: fixation of long bones may be required to treat or prevent pathological fracture. Radiotherapy, if required, is better given post operatively once healing has occurred rather than pre-operatively. Bisphosphonates: The long-term use of bisphosphonates is recommended. General measures: It is important to maintain mobility as immobility increases bone loss and the risk of infection as well as impairing quality of life. Physiotherapy and aids such as spinal supports may be useful.
Hyperviscosity: High levels of paraprotein can lead to increased plasma viscosity.	Symptomatic patients should be treated urgently with plasma exchange; isovolaemic venesection may be used if plasma exchange facilities are not immediately available. If transfusion is essential exchange transfusion should be performed. Chemotherapy should be instituted promptly.
Spinal cord compression: Malignant infiltration of the vertebrae and/or paravertebral tissues can cause spinal cord compression.	Management requires emergency hospital admission and investigation with MRI scanning to define the site and extent of tumour. CT scanning is less satisfactory but may be used if MRI is unavailable or contra-indicated. Dexamethasone should be commenced immediately. Local radiotherapy is the treatment of choice; there is no advantage in outcome for surgical treatment in the absence of spinal instability. Spinal surgery in myeloma patients may be difficult because of osteoporosis but may be indicated for spinal instability.
Infection: Patients with multiple myeloma are immunosuppressed as a result of both the disease & its treatment.	Arrangements should be in place to ensure 24 hour access to specialist team advice for either the patient or for the primary care team. Admission for intravenous antibiotic therapy is usually needed for severe systemic infection. Influenza vaccination should be given to myeloma patients annually in primary care in line with NHS recommendations. Pneumococcal & Haemophilus vaccinations may be given to myeloma patients although there is no evidence of their efficacy in multiple myeloma patients. Prophylactic immunoglobulin infusions have not been shown to improve overall survival but offer some protection against serious infections and reduce the risk of recurrent infections (Chapel et al, 1994).
Anaemia	Discussed in detail in the text.
Psychological Problems	Depression and anxiety occur and should be actively managed with appropriate referral to psychiatric / psychological services.

Anaemia

Anaemia is present in two thirds of patients at presentation and becomes more common in patients with recurrent or progressive disease. Mild to moderate anaemia is common during chemotherapy. Contributing factors should be sought if the anaemia is unexpectedly severe. Red cell transfusion must be given with caution in patients with high paraprotein levels because of the risk of exacerbating hyperviscosity. Anaemia usually improves with response to therapy.

Traditionally, symptomatic anaemia has been managed by red cell transfusion. There is now a growing body of evidence for the efficacy of recombinant human erythropoietin (EPO) in the treatment of chemotherapy related anaemia in a number of cancers, including myeloma. It has been shown to improve Hb and reduce transfusion requirement in patients without renal impairment in randomised controlled trials.

Patients with myeloma were included in two large placebo-controlled trials of EPO in anaemic patients receiving chemotherapy for non-myeloid malignancies (Glaspy et al, 1997; Demetri et al, 1998), each involving over 2,000 patients. Both studies reported significant improvements in Hb level, decreases in transfusion requirements and improvements in patient-assessed quality of life in patients receiving EPO. These benefits were independent of tumour type or response to chemotherapy.

In a study of EPO versus no EPO in 121 patients with myeloma or non-Hodgkin's lymphoma, Osterborg et al (1996) found an improvement in Hb level and elimination of transfusion requirement in 60% of patients on EPO compared with 24% of the control group. In a double-blind placebo-controlled trial in 145 myeloma patients, Dammacco et al (2001) also observed a rise in Hb and decrease in transfusion requirements in patients receiving EPO. Hb levels increased by a mean of 1.8g/dl in patients receiving EPO and 28% required transfusion during the first 3 months of treatment as compared with no rise in Hb levels and a 47% incidence of transfusion requirement in patients receiving placebo. As well as improved levels of Hb and haematocrit, significant improvements in patient-assessed quality of life have been demonstrated with EPO therapy (Glaspy et al, 1997; Demetri et al, 1998; Dammacco et al, 2001).

Currently there are no reliable predictors of response to EPO. With appropriate dosage >80% of patients show an Hb increment of >1g/dl after 4 weeks EPO therapy and improved quality of life is recorded in responding patients (Demetri et al, 1998).

To date there have been no cost-benefit analyses comparing the use of EPO therapy and red cell transfusion in patients with myeloma. However, when considered in comparison with the increasing total costs relating to red cell transfusion as well as the risks of transfusion, a therapeutic trial of 4-6 weeks of EPO appears justifiable for patients with symptomatic anaemia. The objective of avoidance of unnecessary red cell transfusion is in line with NHS strategy encompassed in the NHS Executive circular on "Better Blood Transfusion" (Health Service Circular, 1998).

Recommendations:

Figure 1. Clinical pathways in the management of multiple myeloma

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