1. All patients should receive the immunizations recommended in Appendix III.

2. Standard chemotherapy 
Chemotherapy is the treatment of choice. Even though a cure is not possible, chemotherapy often offers satisfactory palliation. The standard treatment for younger fit patients (up to approximately 70 years of age) is high dose chemotherapy and autologous hematopoietic stem cell transplant. Patients who are candidates for high dose chemotherapy and stem cell transplantation (see section 3 below) should NOT be treated with melphalan prior to stem cell collection because this may make it impossible to gather adequate stem cells to support transplantation. Such patients should be discussed with a member of the Bone Marrow Transplant Team shortly after the diagnosis is made. For older or unfit patients who are not eligible for transplantation, melphalan based treatment such as melphalan prednisone and bortezomib (UMYMPBOR) or melphalan, prednisone and thalidomide (UMYMPT) is used.

3. Hematopoietic stem cell transplantation

In co-operation with the Lymphoma Tumour Group, the Bone Marrow Transplantation Team offers treatment with high dose chemotherapy and hematopoietic stem cell transplantation to selected patients up to approximately 70 years of age. These patients will receive induction chemotherapy that includes dexamethasone and bortezomib (UMYBORPRE). It is recommended that cyclophosphamide also be added in combination to deepen the remission prior to transplant. Physicians with potentially eligible patients should initiate referral with a member of the Bone Marrow Transplant Team. Patients who are candidates for high dose chemotherapy and hematopoietic stem cell transplantation should NOT be treated with melphalan because this may make it impossible to gather adequate stem cells to support transplantation.

4. Bisphosphonates 

Third generation bisphosphonates are effective in preventing some of the skeletal destruction caused by myeloma (Berenson, NEJM, 1996;334:488). Intravenous pamidronate, 30 mg in 500 mL saline over 1 h, once every 4 to 6 weeks, should be given to all patients receiving chemotherapy for myeloma (MYPAM). In order minimize the risk of osteonecrosis or renal toxicity, the duration of pamidronate treatment should be kept to the time shown in the randomized trial to have been beneficial. For patients who undergo high dose chemotherapy and stem cell transplantation Pamidronate should be continued at approximately monthly intervals until assessment of response. Most patients reach a complete or very good partial response in which case Pamidronate should be stopped; otherwise, continued for 24 months then stop. For patients who do not undergo a stem cell transplant Pamidronate should be continued for 24 months then stopped. After the pamidronate is stopped, it should only be resumed, for another 24 month course if the myeloma again requires systemic treatment. Prior to the initiation of bisphosphonates, patients should have a proper dental examination and have acute dental problems addressed to avoid the risk of osteonecrosis of the jaw. All patients treated with bisphosphonates should be provided with guidelines for dental care.

5. Secondary chemotherapy 
Secondary treatments for recurrent myeloma include the following:

• Lenalidomide and Dexamethasone (UMYLENDEX)
• Bortezomib with Dexamethasone (UMYBORREL)
• Thalidomide (MYTHALID) (currently drug funding is not available with the BCCA)

The choice of the timing and order of these drugs must be individualized. Active clinical research is being conducted for treatment of relapsed/refractory myeloma. Members of the Leukemia/BMT Program or BCCA staff should be contacted about the status of such investigations.

6. No initial therapy 
Rarely, multiple myeloma is asymptomatic and either progressing slowly or remaining static. Hence, therapy may be initially withheld in patients who fulfil all of the following criteria. Such patients do not need to be treated with bisphosphonates.

• No symptoms
• Satisfactory peripheral blood counts
• No paraprotein in the urine
• Normal serum calcium
• Stable serum paraprotein level
• No non-irradiated lytic bone lesions
• No renal or neurological disease due to myeloma
• No more than one lytic bone lesion

7. Radiation 
Local radiation should be considered for patients with any of the following:

• A symptomatic lytic bone lesion or soft tissue plasmacytoma which is not responding to systemic treatment
• Threatening or actual pathological fracture
• Spinal cord compression (recall that spinal cord compression is an emergency; a radiation oncologist should be contacted immediately to discuss treatment plans)

8. Renal Impairment in Multiple Myeloma
Renal impairment occurs in up to 25% of patients upon presentation. Damage to the renal tubules is caused by free light chains. Other causes which contribute to renal impairment include dehydration, hypercalcemia, nephrotoxic drugs (such as NSAIDS) and infections. Patients presenting with renal failure have higher early death rate and worse overall prognosis. Renal impairment may be the initial manifestation of multiple myeloma for which reason, patients should be worked up for myeloma should they present with renal impairment. A renal biopsy should also be considered. Early diagnosis and treatment can influence the degree and the ability to reverse renal impairment and the ability to administer anti-myeloma medication.

Initial measures to control and reverse renal impairment include:

• Vigorous rehydration
• Discontinuation of nephrotoxic drugs
• Treatment of precipitating factors (eg. Hypercalcemia, hyperuricemia and infections)

Once myeloma is suspected or diagnosed treatment should be initiated as soon as possible. The following are recommended:

• Dexamethasone. Appropriate doses are 20-40mg po daily for 4 days. This can be started immediately.
• Bortezomib: Dose adjusting is not necessary in renal impairment. Approval through the Compassionate Access Program (CAP) is required. For patients who will not be eligible for transplant due to age and fitness an application for bortezomib should be made through the UMYMPBOR protocol. For patients who may be eligible for transplant application for bortezomib should be made through the UMYBORPRE protocol.
• Consultation with the nephrology service to guide renal management