Treatments for multiple myeloma

Standard treatment options include:

• Targeted therapy. Targeted drug treatments focus on specific weaknesses present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die.
• Immunotherapy. Immunotherapy uses your immune system to fight cancer. Your body’s disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that help them hide from the immune system cells. Immunotherapy works by interfering with that process.
• Chemotherapy. Chemotherapy uses drugs to kill cancer cells. The drugs kill fast-growing cells, including myeloma cells. High doses of chemotherapy drugs are used before a bone marrow transplant.
• Corticosteroids. Corticosteroid medications regulate the immune system to control inflammation in the body. They are also active against myeloma cells.
• Bone marrow transplant. A bone marrow transplant, also known as a stem cell transplant, is a procedure to replace your diseased bone marrow with healthy bone marrow.

Before a bone marrow transplant, blood-forming stem cells are collected from your blood. You then receive high doses of chemotherapy to destroy your diseased bone marrow. Then your stem cells are infused into your body, where they travel to your bones and begin rebuilding your bone marrow.

• Radiation therapy. Radiation therapy uses high-powered energy beams from sources such as X-rays and protons to kill cancer cells. It may be used to quickly shrink myeloma cells in a specific area — for instance, when a collection of abnormal plasma cells form a tumor (plasmacytoma) that’s causing pain or destroying a bone.

Modern Treatment of Myeloma

As myeloma is incurable, the intention of treatment is to prolong the remission and delay the onset of relapse with the least amount of side effects. With more novel drugs coming onstream, there is big paradigm shift in how myeloma is being treated today. Predicated on our improved understanding of the disease biology, the focus now is not hitting the disease hard, but hitting it smart with new drugs in the armamentarium. Patients are benefiting from the significantly improved treatment options that have emerged in the past decade that improve survival rates and decrease pain and complications such that myeloma is now more akin to a chronic disease where patients can survive 10 years or more than a terminal cancer. Importantly, older patients now have a chance to defy the natural history of multiple myeloma as newer targeted drugs are better tolerated and have better side effect profiles.

The development of the proteasome inhibitor bortezomib in the past decade represented a major advance in multiple myeloma therapy. This was predicated on the discovery of the proteasome, the ‘garbage bin’ of the cell. Disrupting this with a proteasome inhibitor results in excessive accumulation of waste products in the cell which would eventually lead to cell death. Myeloma cells are most susceptible to proteasome inhibition. The success of bortezomib led to the development of the next-generation proteasome inhibitor called carfilzomib which is more potent than bortezomib. This drug was approved by the FDA in 2012 and it plays an important role in salvaging patients when the disease relapses.

Immunomodulatory drugs like thalidomide, lenalidomide and the next-generation pomalidomide have also resulted in significant improvement outcomes for multiple myeloma patients as well. They are highly effective in stimulating the patient’s immune system to fight the myeloma cells. Results from various clinical trials demonstrate that having these 2 classes of drugs in the myeloma armamentarium doubles the survival rate of many patients. Their introduction has tremendously lowered the reliance on conventional chemotherapy to treat the disease.

The latest excitement in the field of myeloma therapeutics is the advent of immunotherapy. This modality harnesses the body’s immune system to effect cancer cell killing. Antibodies are substances produced by the immune system to fight off viruses, bacteria and other foreign substances. Myeloma researchers have found ways to produce synthetic antibodies in the lab, and these antibodies can help enhance the patient’s own immune system response and target myeloma cells. One such monoclonal antibody, daratumumab was initially approved for the treatment of relapsed multiple myeloma in 2015 and due to its impressive effect in eradicating myeloma cells, it was recently approved as the frontline standard of care for multiple myeloma. When daratumumab is combined with a proteasome inhibitor and/ or immunomodulatory agent in the frontline, the remission duration achieved can now be as long as what a stem cell transplantation can accord. Elotuzumab is another approved antibody directed against a protein on the myeloma cell surface.

Belantamab mafodotin is an antibody-drug conjugate (ADC), a type of precision cancer agent that targets specific proteins on the myeloma cell surface with an antibody. The antibody is in turn attached to a cancer cell killing agent that is then internalized following attachment of the antibody to the cancer cell and this causes the cancer cell to die when the toxic effect of this ‘smart bomb is unleashed.

Cellular Immunotherapy is the latest modality to be approved recently in the treatment of myeloma. Chimeric antigen receptor therapy (CAR-T) involves extracting a patient’s T cells which are the immune system’s “defender cells,” responsible for finding and eliminating abnormal cells throughout the body. These T cells are then modified to recognize multiple myeloma cells as dangerous intruders and then reintroduced into the patient’s body to help fight the cancer. Data from clinical trials have shown spectacular results with the use of CAR-T in patients who have failed all standards of care.

Treatment for multiple myeloma is now always tailored to the specific stage of the disease and the patient’s age, kidney function, overall health status, and other needs. Often treatment involves a combination of various novel pharmacologic agents alluded above.