What are multiple myeloma medications?

Multiple myeloma medications are prescribed to treat multiple myeloma (MM), a cancer of plasma cells in the bone marrow. Chemotherapy, targeted therapy, immunotherapy, corticosteroids and symptom control medications.
Multiple myeloma medications are prescribed to treat multiple myeloma (MM), a cancer of plasma cells in the bone marrow. Chemotherapy, targeted therapy, immunotherapy, corticosteroids and symptom control medications.

Multiple myeloma medications are prescribed to treat multiple myeloma (MM), a cancer of plasma cells in the bone marrow. Plasma cells are immune cells which produce antibodies to fight infections in the body.

Several classes of medications are used to control the progression of multiple myeloma and treat complications that arise from the condition. Multiple myeloma medications include:

  • Chemotherapy drugs that destroy cancer cells
  • Targeted therapies which target specific cell proteins or signaling pathways to slow cancer growth and spread
  • Immunomodulatory medications which act on the immune system
  • Corticosteroids for rapid control of cancer
  • Medications to manage MM symptoms and complications

Chemotherapy drugs are an integral part of multiple myeloma treatment. Commonly prescribed chemotherapy medications for MM include melphalan and vincristine. Antiemetic drugs to prevent side effects such as nausea and vomiting are often prescribed with chemotherapy.

Targeted therapy medications are formulations of monoclonal antibodies or small molecule drugs. Monoclonal antibodies are biological, lab-produced proteins which can be designed to directly inhibit and/or kill myeloma cells or help the immune system kill them. Daratumumab and elotuzumab are examples of monoclonal antibodies used to treat multiple myeloma.

Small molecule drugs are microscopic particles that suppress cancer growth by interacting with proteins in the cancer cells and modifying their activity. Small molecule drugs such as bortezomib are a part of first-line therapy for multiple myeloma.

Immunomodulatory drugs such as thalidomide and lenalidomide are used to inhibit inflammation, help the immune system kill the myeloma cells, and prevent new blood vessel formation (angiogenesis) in the myeloma tumors.

Corticosteroids constitute an essential part of MM medication regimen for rapid control of cancer growth, and for reducing pain, inflammation and chemotherapy side effects. Bone pain may be treated with pain relievers, in addition.

Other medications prescribed for MM treat complications that follow MM. Two primary complications of MM are bone loss and anemia, which are respectively treated with bisphosphonates and erythropoietin, a naturally occurring hormone that stimulates red blood cell growth.

What is multiple myeloma?

Multiple myeloma is a malignant type of blood cancer that develops in plasma cells in the bone marrow, a spongy tissue in the core of many bones. Cancers are a group of diseases in which abnormal cells grow out of control. Cancers which spread to other parts of the body are termed malignant, or metastatic.

Plasma cells are immune cells that produce antibodies to fight infections. White cells (lymphocytes) are the primary cells in the immune system, which include T cells and B cells. In response to infections, B cells mature into plasma cells and produce antibodies to the pathogen, which help the killer T cells identify and kill the infected cells.

All the blood cells such as red cells, white cells and platelets grow in the bone marrow. The overgrowth of cancerous plasma cells suppresses the growth of normal blood cells in the bone marrow, causing blood disorders and low immunity to infections.

Myeloma cells grow into multiple masses known as tumors, which form lesions (myeloma) on the bones and weaken them. Myeloma is named multiple myeloma because most patients have multiple tumors at the time of diagnosis.

Myeloma cells not only multiply uncontrollably, but also produce large quantities of a single type of antibody known as monoclonal paraprotein (M protein). M protein does not help fight infection as healthy antibodies do. Buildup of M protein in the blood can damage organs such as kidneys.

Multiple myeloma symptoms and complications

The symptoms and complications of multiple myeloma include the following:

  • Bone complications

Bone lesions which cause some of the first MM symptoms such as:

Spinal cord compression from bone damage with symptoms such as:

Breakdown of bone cells which releases calcium and causes high blood calcium levels (hypercalcemia) with symptoms such as:

Other complications

  • High blood viscosity from increased levels of M proteins, which restricts blood flow in the tiny blood vessels (capillaries) resulting in reduced oxygen supply to the tissues. 
  • Kidney damage from excess M proteins and calcium in blood.
  • Amyloidosis, a condition in which fragments of proteins known as light chain amyloids get deposited on organs and affect their function.
  • Neurological symptoms such as carpal tunnel syndrome.

Myeloma classification

Multiple myeloma is a stage in the spectrum of plasma cell diseases. Classification of the disease plays an important role in determining the stage of the disease and designing appropriate treatment. Plasma cell diseases are broadly classified as follows:

  • Monoclonal gammopathy of undetermined significance (MGUS): MGUS is considered a premalignant abnormal cell growth (neoplasm). A small amount of M protein is found in blood, but tumor growth and other symptoms of myeloma are absent. MGUS rarely develops into MM, but MM is almost always preceded by MGUS.
  • Solitary plasmacytoma: Solitary plasmacytoma is the growth of a single malignant myeloma tumor inside or outside the bone, or in other organs which is known as extramedullary plasmacytoma. Solitary plasmacytoma can recur and progress to multiple myeloma. 
  • Indolent and smoldering multiple myeloma: Indolent and smoldering multiple myeloma are premalignant stages of multiple myeloma, marked by slightly high count of plasma cells in the bone marrow and M protein in the blood. Myeloma symptoms such as bone lesions and anemia are mild or absent. Many people eventually progress to active MM.
  • Active multiple myeloma: In active multiple myeloma, plasma cells constitute more than 30% of blood cells in the bone marrow, and M protein levels are high in blood and urine. Most MM patients have multiple bone lesions, bone pain, anemia and other symptoms at the time of diagnosis.

SLIDESHOW

Understanding Cancer: Metastasis, Stages of Cancer, and More See Slideshow

What causes multiple myeloma?

As with most cancers, the exact cause of multiple myeloma isn’t established, but many factors are thought to play a role. Genetic mutations can make certain growth-promoting and tumor-suppressing genes run out of control and turn into cancer-causing genes (oncogenes). Studies on MM have found abnormalities in oncogenes such as MYC, RAS and p53 genes.

Genetic mutations in MM may be composed of a missing and/or extra chromosome. Studies have found parts of chromosome 17 often missing in myeloma cells. In some people, two chromosomes have swapped places (translocation).

In some cases, MM may develop because of excessive production of an inflammatory protein (cytokine) known as IL-6 by dendritic cells, which are one of the types of immune cells in the bone marrow.

The incidence of multiple myeloma appears higher in males and African Americans. Additional possible risk factors for multiple myeloma include:

  • Presence of MGUS, plasmacytoma or smoldering multiple myeloma
  • Advanced age
  • Obesity
  • Radiation exposure
  • Occupational exposures to chemicals in agriculture (herbicides and insecticides) and petrochemical industries
  • Human herpes virus 8 infection of dendritic cells in the bone marrow.

Is multiple myeloma cancer curable?

Currently, there is no cure for multiple myeloma, but the cancer can be successfully managed with treatment to limit cancer growth and spread, reduce the severity of symptoms and prolong survival.

Many new medications have been approved by FDA in the recent years and the search for safer and more effective therapies continues. The five-year survival rate in MM has gone up from 34.6% in 1998 to 53.9% in the most recent statistics for the period 2010 to 2016.

What is the best treatment for multiple myeloma?

Treatment for multiple myeloma is individualized based on the stage of disease and severity of symptoms. Treatment often involves a combination of therapies.

Monoclonal gammopathy of undetermined significance does not require treatment, only regular checkups to ensure multiple myeloma doesn’t develop. Solitary plasmacytoma can often be successfully treated with radiotherapy.

In the case of smoldering multiple myeloma, the practice has been to ‘wait and watch,’ with regular checkups, but several studies are ongoing to evaluate if early preventive treatment with immunotherapy and targeted therapy might stop its progression to active multiple myeloma in high-risk smoldering myeloma patients.

Treatments for multiple myeloma include:

  • Medications: Systemic therapies with medications such as chemotherapy, targeted therapy and immunotherapy are the mainstay treatments for active multiple myeloma. Medications are also the primary treatment for MM complications.
  • Radiotherapy: Radiotherapy is the use of high-energy X-rays to kill the myeloma cells. Radiation is performed if the pain is mild and less than 50% of bone is affected.
  • Stem cell transplantation: Stem cells are harvested from the patient’s own blood and infused back (autologous transplant) after destroying the myeloma cells with chemotherapy and radiation. In selected patients, especially in twins, donor stem cells (allogenic transplant) may be used.
  • Surgery: Surgical care is primarily for treating complications from bone loss and lesions, procedures to prevent or fix fractures, and relieve spinal compression.
  • Plasmapheresis: Plasmapheresis is a procedure used to filter out the M protein in the blood. The patient’s blood passes through a device in which the M protein gets removed and the blood is reinfused.

What is the latest treatment for multiple myeloma?

One of the latest therapies for multiple myeloma is known as CAR T-cell immunotherapy, a kind of targeted therapy. The patient’s immune cells are extracted and genetically modified to identify and bind to a specific protein on the myeloma cells. 

When reinfused, these modified immune cells activate the immune system to kill the myeloma cells.

The latest such medication approved by FDA in 2020 is belantamab mafodotin-blmf. This medication is a genetically modified antibody that targets a protein known as BCMA on the myeloma cells, but it also carries a drug to directly kill them. Researchers are studying more immune mechanisms that can be targeted.

In addition, many new combinations of different classes of drugs are being evaluated for use in multiple myeloma. It is also possible for multiple myeloma patients to enroll in clinical trials for new drugs. Some latest medications that are being studied for use in MM include the following:

  • Melphalan flufenamide (Melflufen) which has been granted priority review by the FDA
  • Venetoclax (Venclexta) which has been approved for chronic lymphocytic leukemia and small lymphocytic lymphoma

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What are the types of multiple myeloma medications?

Several classes of medications are used to treat multiple myeloma and typically a combination of medications are prescribed depending on the stage of the disease. Multiple myeloma medications are systemic therapies which are administered orally or through injections and infusions. Medications for multiple myeloma fall into two categories:

  • Anti-cancer medications to treat the primary cancer, which include:
    • Chemotherapy medications
    • Targeted therapy medications which include:
      • Proteasome inhibitors
      • Histone deacetylase inhibitors
      • Nuclear export inhibitors
      • Monoclonal antibodies
      • Anti-B-cell maturation antigen (BCMA) antibodies
    • Immunomodulatory medications
    • Corticosteroids
  • Medications for complications which include:
    • Bone-related:
      • Bisphosphonates
      • Monoclonal antibodies
    • Blood-related:
      • Erythropoiesis stimulation agents

How do multiple myeloma medications work?

Anti-cancer medications

Chemotherapy

Chemotherapy medications kill myeloma cells by preventing cell growth, and replication of DNA during cell division. Chemotherapy drugs are largely toxic to all cells in growth phases, including healthy cells. The choice of chemotherapy drug depends on the patient’s condition, age, kidney function and likelihood of receiving stem cell transplantation.

Chemotherapy treatments are usually given in cycles lasting three to four weeks and one course of treatment typically consists of four to six cycles. Chemotherapy drugs approved by FDA for treating multiple myeloma are:

Melphalan hydrochloride (Alkeran, Evomela)

Chemotherapy drugs used as part of combination therapies for multiple myeloma include:

  • Doxorubicin hydrochloride
  • Etoposide
  • Cisplatin
  • Vincristine sulfate

Targeted therapy

Targeted therapy medications do not kill cancer cells, but alter their functions to inhibit myeloma growth and spread. Each targeted therapy medication works in a unique way to block the activity of specific proteins which help cancer cells grow, divide, migrate to other parts, differentiate into specialized cells, and evade programmed cell death.

Targeted therapy medications include:

  • Proteasome inhibitors

Proteasome inhibitors are small molecule drugs that block the activity of proteasome. Proteasome is an enzyme which helps cells break down the proteins they require for division. Myeloma cells are particularly vulnerable to proteasome inhibitors, because they produce a lot of protein.

FDA-approved proteasome inhibitor for treating multiple myeloma is:

FDA-approved proteasome inhibitor (alone or in combination with other drugs) for multiple myeloma that has relapsed or hasn’t responded (refractory) to at least one other treatment include:

  • Carfilzomib (Kyprolis)
  • Ixazomib citrate (Ninlaro)

Histone deacetylase inhibitors

Histone deacetylase inhibitors make the myeloma cell DNA more accessible to transcription and alteration with targeted therapy. Histone deacetylase inhibitors block the activity of histone deacetylase, an enzyme that helps histone protein keep the DNA tightly coiled.

FDA-approved histone deacetylase inhibitor for multiple myeloma patients who have had at least two other standard treatments is:

  • Panobinostat lactate (Farydak) 

Nuclear export inhibitors

Nuclear export inhibitors promote myeloma cell death by blocking the activity of a protein known as exportin 1 (XPO1). XPO1 helps carry proteins from the cell nucleus to other parts of the cell which need the proteins to keep the cell functioning and alive.

The FDA-approved nuclear export inhibitor for relapsed or refractory multiple myeloma that hasn’t responded to at least four other targeted therapies is:

  • Selinexor (Xpovio)

Monoclonal antibodies

Monoclonal antibodies developed to treat multiple myeloma bind to two specific proteins, CD38 and SLAMF7, found on the surface of myeloma cells and mark them for destruction by the T cells in the immune system. Monoclonal antibodies approved by FDA for multiple myeloma are:

  • Anti-CD38
  • Approved for newly-diagnosed, relapsed or refractory MM:
    • Daratumumab (Darzalex) 
    • Daratumumab hyaluronidase-fihj (Darzalex Faspro)
  • Approved for patients who have received at least two other treatments:
    • Isatuximab-irfc (Sarclisa) 
    • Anti-SLAMF7
  • Approved for MM patients who have received at least one other treatment:
    • Elotuzumab (Empliciti) 

Anti-B-cell maturation antigen (BCMA) antibodies

Anti-BCMA antibodies are a new class of drugs known as antibody-drug conjugates. Anti-BCMA antibodies bind to the BCMA protein on the myeloma cell surface and deliver a toxic drug which kills them. BCMA proteins are found on normal B-cells as well as myeloma cells.

Anti-BCMA antibody approved by FDA to treat relapsed or refractory MM in patients who have received at least four other targeted therapies is:

  • Belantamab mafodotin-blmf (Blenrep)

Immunomodulatory medications

Immunomodulatory medications are an integral part of multiple myeloma medication regimens and typically prescribed in combination with a corticosteroid. These medications suppress pro-inflammatory responses, prevent new blood vessel formations in the tumors and also directly kill myeloid cells.

FDA-approved immunomodulatory medications for multiple myeloma include:

  • Thalidomide (Thalomid) for newly diagnosed MM, available only as a part of a special program called Thalomid REMS, because of toxicity concerns
  • Lenalidomide (Revlimid) as maintenance therapy after autologous stem cell transplant
  • Pomalidomide (Pomalyst) for patients who have received at least two other therapies

Corticosteroids

Corticosteroids are an important part of multiple myeloma treatment. High doses of corticosteroids can kill myeloma cells and can be used for short periods to rapidly decrease myeloma cell population. Corticosteroids are powerful anti-inflammatory agents that can reduce pain, and are also used along with chemotherapy, immunotherapy and targeted therapy to reduce side effects.

Corticosteroids commonly used in multiple myeloma include:

Combination medication regimens

Multiple myeloma treatment typically requires a combination of two or three medications. The choice of medications and dosage depend on the treatment phase, which may be:

  • Induction phase to rapidly control the cancer and relieve symptoms
  • Consolidation phase which targets elimination of cancer
  • Maintenance therapy to prolong the period of remission
  • Commonly prescribed combination medication regimens for MM include:
  • Lenalidomide/dexamethasone
  • Carfilzomib/lenalidomide/dexamethasone
  • Bortezomib/cyclophosphamide/dexamethasone
  • Daratumumab/lenalidomide/dexamethasone
  • Bortezomib/liposomal doxorubicin/dexamethasone
  • Panobinostat/bortezomib/dexamethasone
  • Elotuzumab/bortezomib/dexamethasone
  • Melphalan/prednisone
  • Melphalan/prednisone/thalidomide or bortezomib
  • Vincristine/doxorubicin/dexamethasone (VAD)
  • Dexamethasone/cyclophosphamide/etoposide/cisplatin (DCEP)
  • Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide/bortezomib (VDT-PACE) 
  • Selinexor/bortezomib/dexamethasone

Medications for complications

Bone medications

Bone medications are prescribed to limit bone damage and loss from multiple myeloma. These also prevent release of calcium from the bones and help bring down blood calcium levels. Two classes of medications have been approved by FDA to treat bone complications from myeloma:

Bisphosphonates

Bisphosphonates work by inhibiting the activity of bone cells known as osteoclasts which break down bone tissue. Bisphosphonates approved by FDA to treat bone loss and hypercalcemia in multiple myeloma are:

Monoclonal antibodies

The monoclonal antibody developed to treat bone loss binds to a protein known as RANKL and prevents the formation of osteoclasts (cells that break down bone). The FDA-approved monoclonal antibody to prevent bone-related complications from multiple myeloma is:

  • Denosumab (Xgeva)
  • Anemia medications

Anemia medications are prescribed to promote red blood cell proliferation (erythropoiesis). The medication used to treat anemia in multiple myeloma is an erythropoiesis stimulating agent, a formulation of a naturally occurring hormone that stimulates division and differentiation of progenitor red cells into mature red cells. The FDA-approved anemia medication is:

Additional information

  • Please visit our medication section of each drug within its class for more detailed information.
  • If your prescription medication isn’t on this list, remember to look on MedicineNet.com drug information or discuss with your healthcare provider and pharmacist.
  • It is important to discuss all the drugs you take with your doctor and understand their effects, possible side effects and interaction with each other.
  • Never stop taking your medication and never change your dose or frequency without consulting with your doctor.

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Understanding Cancer: Metastasis, Stages of Cancer, and More See Slideshow

Treatment & Diagnosis

Medications & Supplements

Medically Reviewed by a Doctor on 4/5/2021

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Medically Reviewed on 4/5/2021
References
https://emedicine.medscape.com/article/204369-medication

https://www.cancer.org/cancer/multiple-myeloma/treating/chemotherapy.html

https://www.cancer.net/cancer-types/multiple-myeloma/types-treatment

https://themmrf.org/multiple-myeloma/treatment-options/standard-treatments/

https://www.cancer.gov/about-cancer/treatment/drugs/multiple-myeloma