Taking part in a clinical trial may be the best treatment choice for some myeloma patients. Clinical trials are under way to develop treatments that increase the remission rate of myeloma or cure the disease. Today's standard treatments for cancer are based on earlier clinical trials. The Leukemia & Lymphoma Society (LLS) continues to invest funds in myeloma research.

Clinical trials can involve new drugs, new combinations of drugs or approved drugs being studied to treat patients in new ways such as new drug doses or new schedules to administer the drugs. Clinical trials are conducted worldwide under rigorous guidelines to help doctors find out whether new cancer treatments are safe and effective or better than the standard treatment.

Current Myeloma Research and Clinical Trials

Below are some types of research and clinical trials under way:

Drugs and Drug Combinations 

Recent advances in the treatment of myeloma have resulted in improved response rates and overall survival in newly diagnosed patients and patients with relapsed myeloma. Eventually, however, nearly all patients experience a relapse of their illness because, with time, myeloma cells become resistant to current drug therapies. This means there is a continuing role for the introduction of investigational agents that overcome drug resistance. Several new approaches, including combination therapies to counteract drug resistance, are being studied in clinical trials for initial treatment and for the treatment of relapsed or refractory myeloma. Some examples are:

• A new proteasome inhibitor named oprozomib is being studied in various clinical trials. It is used in combination with dexamethasone, for treating either newly diagnosed patients or patients with relapsed or refractory myeloma.
• High-dose carfilzomib (Kyprolis®), a proteasome inhibitor, is being evaluated to be given in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed myeloma.
• The drug venetoclax (Venclexta™) is a BCL-2 inhibitor that is FDA approved to treat CLL patients who have a chromosomal abnormality called “17p deletion.” It is being studied in clinical trials, as part of combination therapy with carfilzomib and dexamethasone, for the treatment of multiple myeloma patients who have received one to three prior lines of therapy.
• An ongoing trial is evaluating the efficacy of the combination ixazomiblenalidomide-dexamethasone compared with placebo-lenalidomidedexamethasone for the treatment of relapsed and refractory myeloma patients.
• The triple-drug combination pomalidomide-bortezomib-dexamethasone is being evaluated in patients with relapsed and refractory multiple myeloma.

Stem Cell Transplantation

A number of approaches are under study, including the use of autologous and nonmyeloablative (reduced intensity) allogeneic stem cell transplantation.

• A current trial is evaluating nonmyeloablative transplant followed by bortezomib for high-risk multiple myeloma patients.
• The role of lenalidomide as maintenance therapy in patients who have received a tandem autologous transplantation is being studied in clinical trials. 

For more information about all types of stem cell transplantation, see the free LLS information booklet, Blood and Marrow Stem Cell Transplantation.

Immunotherapy

Various forms of immunotherapy are being studied, including:

• Dendritic Cell/Tumor Fusion Vaccines. Proteins on the surface of myeloma cells may be especially well-suited targets for attack by vaccines. Dendritic cells are generally found in small amounts in the body and are responsible for immune responses against “foreign” substances. To create these fusion vaccines, cells are removed from the patient’s tumor and fused (mixed) with dendritic cells obtained from the blood, in order to stimulate a powerful antitumor response. This type of immunotherapy is being evaluated in clinical trials for both newly diagnosed and previously treated patients.
• Monoclonal Antibodies. These immunotherapy agents are increasingly being used to treat myeloma patients both to target the cancer cells directly and to modulate the patient’s immune system. While some monoclonal antibodies (“naked” antibodies) work by themselves, others are joined with a chemotherapy drug or attached to a radioactive particle and are known as “conjugated monoclonal antibodies.”
  • A promising example of this therapy, currently being studied in clinical trials, is the monoclonal antibody indatuximab ravtansine (BT062). This antibody, when coupled with a radioactive isotope, targets the CD138 antigen expressed in greater than 95 percent of myeloma cells.
  • Isatuximab, an investigational anti-CD38 monoclonal antibody, is being studied for the treatment of patients with relapsed and refractory multiple myeloma. The trial will compare isatuximab in combination with pomalidomide and dexamethasone against pomalidomide and dexamethasone.
  • Milatuzumab is an anti-CD74 monoclonal antibody that is being evaluated, in combination with doxorubicin, for patients with relapsed and refractory myeloma.
  • Ulocuplumab (BMS-936564) which targets CD184 is under investigation in patients with relapsed and refractory myeloma, in combination with either lenalidomide and dexamethasone or bortezomib and dexamethasone.
  • Denosumab (Xgeva®) is a monoclonal antibody that has been approved to treat osteoporosis in postmenopausal women and also to treat bone-related disease in patients with prostate or breast cancer. It is being evaluated in clinical trials for the prevention of bone fractures in multiple myeloma.
• Programmed Death (PD-1) Checkpoint Inhibitors. A vital part of the immune system is its ability to distinguish healthy cells in the body from those that it recognizes as foreign or harmful. The immune system depends on multiple checkpoints—molecules on certain immune cells that need to be activated (or turned off) in order to start an immune response. Cancer cells sometimes take advantage of these checkpoints to escape the detection of active immune cells. PD-1 is a checkpoint protein that is found on the surface of T cells. It normally acts as a type of “off switch” that helps keep immune cells from attacking healthy cells in the body. It accomplishes this when it attaches to a PD-L1, a protein found on some normal cells and also in some cancer cells. When PD1 binds to PD-L1, a message is sent to the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1 receptors, which help them avoid an immune attack.
  Checkpoint inhibitors are drugs created to target the PD1 or PD-L1, blocking their actions, and allowing the immune system to recognize and eliminate cancer cells. The checkpoint inhibitor pembrolizumab (Keytruda®) is being studied, in combination with pomalidomide and low-dose dexamethasone, for the treatment of refractory and relapsed multiple myeloma. Another clinical trial is examining the performance of pembrolizumab, in conjunction with lenalidomide and dexamethasone, and given post autologous stem cell transplantation, for the treatment of high-risk multiple myeloma.
• Chimeric Antigen Receptor (CAR) T-Cell Therapy. This is a type of immunotherapy that consists of engineering a patient’s own immune cells to recognize and then attack cancerous tumors. This approach has shown very promising results in patients with blood cancers. The patient’s T cells are genetically engineered to produce receptors on their surface called “chimeric antigen receptors (CARs).” The receptors recognize and bind to a specific target found on the cancer cells. In an ongoing clinical trial, which has shown impressive preliminary results, researchers are studying the role of a new B-cell maturation antigen (BCMA) CAR T-cell therapy for patients with relapsed or refractory multiple myeloma

Related Links

• Work one-on-one with an LLS Clinical Trial Specialist who will personally assist you throughout the entire clinical-trial process.