Immunotherapies and Antibodies
Immunotherapy is the newest approach to multiple myeloma treatment. It is an umbrella term that describes different ways to stimulate the immune system and enhance its ability to attack cancer cells. Many of these treatments involve antibodies that target specific proteins found on multiple myeloma cells. These drugs are still in clinical trials but show considerable promise.
These refer to specific antibodies made from identical immune cells that are all clones from the same parent cell. There are a wide variety of monoclonal antibodies targeting different proteins.
Anti-CD 38 inhibitors are monoclonal antibodies targeting the CD38 protein. The CD38 protein is significant because it is often found on the surface of multiple myeloma cells. Targeting this protein results in the death of myeloma cells.
Checkpoint inhibitors are monoclonal antibodies that target proteins found on the immune system’s T cells. T cells are important in eliminating cancer cells and virus-infected cells. There are a number of proteins on T cells that serve as “checkpoints,” allowing the cells to be turned on and off as needed. Checkpoint inhibitors work by either blocking molecules that inhibit T cell activity or by activating those that stimulate a response. In these two ways, checkpoint inhibitors “take the brakes off the immune system,” harnessing its full power to attack cancer cells. Multiple trials of such drugs are in their early stages in multiple myeloma.
Darzalex™ (daratumumab, Genmab/Janssen) is an anti-CD 38 monoclonal antibody.In 2015, Darzalex was approved for use in the treatment of patients with myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor and an IMiD, or whose disease is refractory to both a proteasome inhibitor and an IMiD.
Another monoclonal antibody, Empliciti™ (elotuzumab, Bristol-Myers Squibb/AbbVie), targets the protein SLAMF7, a protein found on myeloma cells in more than 95 percent of people with multiple myeloma, making it an excellent target for treatment. In 2015, Empliciti was approved for use in combination with Revlimid and dexamethasone for the treatment of patients with myeloma who have received one to three prior therapies.
Empliciti, which was studied in Multiple Myeloma Research Consortium (MMRC) trials, works by activating natural-killer mechanisms in the immune system, and it has been effective in both newly diagnosed patients and those who have relapsed. Empliciti has been shown to be most effective when combined with an IMiD and a steroid.
The checkpoint inhibitor Keytruda® (pembrolizumab, Merck) is being evaluated in several clinical trials in myeloma. Keytruda is directed against the PD-L1 (programmed death ligand 1) marker and is already approved for use certain patients with melanoma or lung cancer. Keytruda is being evaluated in a Phase III trial in combination with Revlimid and dexamethasone in newly diagnosed myeloma and in a Phase III trial in combination with Pomalyst® (pomalidomide, Celgene) and dexamethasone in relapsed/refractory myeloma.
Other checkpoint inhibitors are in early phase studies in myeloma.
Vaccines work by stimulating an immune response against tumor-specific antigens, or substances that the body considers foreign. Several vaccines are being evaluated in clinical trials in myeloma. For example, one vaccine is being tested in patients already on an IMiD who are near remission to see if this added treatment improves outcomes.
A second vaccine in clinical trials is targeting the MAGE-A3 protein, which is frequently found on the surface of multiple myeloma cells in high-risk patients. The goal of this vaccine is to help train the immune system to recognize, attack, and kill myeloma cells with this protein.
Adoptive T-cell therapy
This new therapeutic approach is being investigated in clinical trials in myeloma and other cancers. With this approach, patients have their T cells removed and activated with chimeric antigen receptors (CARs). CARs are proteins that allow T cells to recognize a specific antigen on tumor cells.
These genetically engineered cells are then reintroduced into the body. If all goes well, they will start multiplying, and with help from the engineered receptor, will locate tumor cells with the targeted antigen and destroy them.
A pilot trial with patients with multiple myeloma who relapsed after their first stem cell transplant and are undergoing a second one is in its early stages. The hope is that these T cells, along with chemotherapy, will jump-start the immune system.