Clinical trials for multiple myeloma treatment

Induction therapy is the first line oftreatment for multiple myeloma that patients receive. Its main goal is the growth control exhibited by cancer cells, to improve the patient’s response to therapy and to allow stem cells to be harvested for transplantation in the second phase. This therapy combines drugs that are administered throughout the body via the bloodstream, known as systemic drug therapy. In this first phase, two or three treatments are usually administered together: 

• Corticosteroid therapy: This treatment uses high doses of steroids to control inflammation by destroying malignant lymphocytes, thereby improving the body’s immune response. Corticosteroids commonly administered include dexamethasone or prednisone. 

• Immunotherapy: This treatment helps the immune system fight cancer by blocking the pathways myeloma uses to evade the body’s immune response. This allows the immune system to identify and destroy cancer cells. Immunotherapies used to treat this disease include: 

• • Immunomodulatory agents: the first such agent used for multiple myeloma was thalidomide, which has a high risk of causing neuropathy, among other adverse effects. Currently, lenalidomine is preferred because it is a more potent version with fewer side effects than thalidomide. 

• • Proteasome inhibitors: these are drugs that work by blocking a cellular structure called the proteasome, which breaks down damaged proteins. In multiple myeloma, these malignant cells overproduce abnormal proteins, which can lead to their uncontrolled proliferation. Proteasome inhibitors cause a build-up of proteins inside the cancer cells, leading to their destruction. Proteasome inhibitors to treat multiple myeloma include bortezomib, ixazomib and carfilzomib.

• • Monoclonal antibodies: Antibodies are proteins produced by the immune system to defend against infection. By creating synthetic versions, also known as monoclonal antibodies, they can be designed to specifically target certain proteins, such as proteins found on the surface of myeloma cells. In this way, these synthetic antibodies can selectively attack cancer cells and aid in the treatment of multiple myeloma. Commonly used monoclonal antibodies include daratumumab, isatuximab and elotuzumab.

• • Nuclear export inhibitor: The nucleus of a cell houses DNA, which is essential for the production of proteins that are necessary for the proper functioning of a cell. The XPO1 protein helps transport other proteins from the nucleus to other parts of the cell. The drug selinexor is a nuclear export inhibitor that blocks the XPO1 protein. In doing so, the myeloma cell cannot transport proteins from its nucleus and, as a result, dies.

  • Biospecific T-cell activators (BiTE): teclistamab is a type of immunotherapy called “BiTE” that attaches to T-cells and the BCMA protein on myeloma cells. It works together with the immune system to fight cancer cells. It is used to treat multiple myeloma that has not responded to the previous 4 other treatments.

• Chemotherapy: Although no longer administered as the main treatment, it is still used in some cases. Chemotherapy destroys malignant cells and inhibits their growth, although it can also affect healthy cells and cause side effects. To improve its effectiveness and minimise adverse effects, it is often combined with new drugs. Chemotherapy drugs administered include cyclophosphamide, etoposide, doxorubicin, melphalan, bendamustine and others. The medical team will rule out the use of some drugs that may cause bone marrow damage, such as melphalan, if the patient is a candidate for autologous transplantation.  

These therapies are often combined with each other to determine the most effective approach to treat multiple myeloma and to reduce adverse effects. In addition, as long as the patient is a candidate, they facilitate the process of autologous stem cell transplantation.