Sandbox: treatment

# Overview
Pharmacological regimes for patients with active (symptomatic) multiple myeloma include steroid therapy, immune modulator therapy, and chemotherapy. Whereas patients with smoldering (asymptomatic) multiple myeloma are managed by observation and undergoing follow up tests every 3 to 6 months. The optimal therapy for active multiple myeloma depends on whether or not a patient is eligible for bone marrow transplantation.
Pharmacologic medical therapy for active multiple myeloma patients who are eligible for a bone marrow transplant include either dexamethasone, lenalidomide, bortezomib, thalidomide, carfilzomib, cyclophosphamide, vincristine, or doxorubicin. In addition to the aforementioned agents, pharmacological regimes used for treatment of active multiple myeloma patients who are not eligible for a bone marrow transplant include either melphalan or prednisone.
Alkylating agents are not recommended among transplant eligible patients, as the toxicity of such agents makes the harvest process of bone marrow stem cell difficult later in the course of the disease.

# Medical Therapy

## Smoldering multiple myeloma
- Patients with smoldering (asymptomatic) multiple myeloma are managed by observation and follow up tests every 3 to 6 months.
- Follow up tests for asymptomatic multiple myeloma patients include:
Laboratory studies such as complete blood count, electrolytes, 24 hour urine collection, electrophoresis, and quantitative immunoglobulin analysis
Imaging studies such as skeletal survey, MRI, and PET scan
Flow cytometry as needed
Bone marrow aspiration and biopsy as needed
- Laboratory studies such as complete blood count, electrolytes, 24 hour urine collection, electrophoresis, and quantitative immunoglobulin analysis
- Imaging studies such as skeletal survey, MRI, and PET scan
- Flow cytometry as needed
- Bone marrow aspiration and biopsy as needed
- Treatment should be differed until such patients develop symptoms.

## Active multiple myeoloma
- The optimal therapy for active multiple myeloma depends on whether or not a patient is eligible for bone marrow transplantation.
- Deciding whether a patient is a candidate for bone marrow transplantation depends on a number of key factors that include:
Type of chromosomal mutation
Age
Presence of current associated diseases
Patient's liver function
Patient's kidney function
- Type of chromosomal mutation
- Age
- Presence of current associated diseases
- Patient's liver function
- Patient's kidney function

### Initial therapy
- Preferred pharmacological regimes for treating bone marrow transplant eligible patients include:
- Bortezomib/dexamethasone
- Bortezomib/dexamethasone/lenalidomide
- Dexamethasone/lenalidomide
- Bortezomib/dexamethasone/doxorubicin
- Bortezomib/dexamethasone/thalidomide
- Bortezomib/dexamethasone/cyclophosphamide
- Preferred pharmacological regimes for treating bone marrow transplant ineligible patients:
- Bortezomib/dexamethasone
- Low dose dexamethasone/lenalidomide
- Melphalan/prednisone/thalidomide
- Melphalan/prednisone/bortezomib
- The VAD regimen (vincristine, adriamycin, and dexamethasone) has shown efficacy ranging from 60 to 80%, in previously treated and untreated patients. This regimen is beneficial in the manner that it avoids early exposure to alkylating agents thus reducing the risks of myelosuppression and further leukemia's, without compromising on efficacy.
- One of the commonly used induction regimens include dexamethasone with lenalidomide and bortezomib for a period of 8 months based on the side effect profile and associated co-morbidities.
- Lenalidomide is orally administered and increases the risk for deep vein thrombosis, while bortezomib is given IV and preferred in patients with abnormal renal function tests.
- Bortezomib is given IV and preferred in patients with abnormal renal function tests.
- Dexamethasone is used alone at a dose of 40 mg for 4 days consecutively, and equals efficacy to that shown by a combination with VAD (vincristine, adriamycin, and dexamethasone).
- Thalidomide: A number of trials were conducted to assess the efficacy of thalidomide as an independent induction agent. All of them found improved response rates with thalidomide and no reduction in stem cell load.
- Alkylating agents are equal in efficacy when combined with VAD regimens, two of the most common ones being melphalan and oral cyclophosphamide plus prednisolone.

### Supportive therapy
- Supportive therapy is recommended based on patient's symptoms and medication's side effect.
- Supportive therapy for active multiple myeloma includes:
- Bisphosphonates to prevent osteoporosis
- Erythropoietin to prevent anemia
- Vaccines to prevent recurrent infections
- Blood thinners to prevent blood clots
- Plasmapheresis to prevent hyperviscosity and renal failure

### Maintenance therapy
- After a few months of induction therapy the advantages of continuing the same therapy seems to be limited.
- Therefore, this phase is being followed up with maintenance therapy with one of the newer agents such as thalidomide, lenalidomide or bortezomib.
- However, further clinical trials are needed to establish the efficacy of each of these agents.

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