Clinical trials and experimental therapies

Almost all cancer treatments available today resulted from research conducted in clinical trials. Clinical trials are critically important to the development of new multiple myeloma treatments, and to helping doctors better understand the disease itself.

For many people with multiple myeloma, participation in a clinical trial may be a good option for treatment. Be sure to talk with your doctor about which clinical trials are available and whether one of them may be right for you.

Here are a few things to know about clinical trials:

  • Broadly, there are three types of clinical trials
    • Phase 1 trials determine safety and dosage, as well as how the drug is absorbed and acts in the body
    • Phase 2 trials evaluate effectiveness and safety
    • Phase 3 trials compare the effectiveness and safety of the new drug with those of standard treatments
  • In addition to the new drugs currently being studied in clinical trials, drugs that have been previously approved to treat other diseases are being examined in clinical trials to determine whether they may be effective for treating multiple myeloma
  • Some patients worry that participating in a clinical trial may mean that they receive only a placebo and no actual treatment. In fact, all patients in a clinical trial receive treatment; one set of patients receives standard treatment (called the standard of care group) and the other set of patients receives the new treatment (called the new treatment group)
  • Doctors and nurses who conduct clinical trials are always the most familiar with the latest research and treatments, and the trials often take place at larger research institutions
    • If you don’t live near the research institution, it may be possible for your care to be conducted in the office of your own oncologist, or your travel may be limited to a small number of visits to the larger institution
  • If you decide to participate in a clinical trial, you will receive a consent form that serves as your guide to all of the important information you need to know about the trial
  • In any clinical trial, you are allowed to quit at any point, for any reason

Interested in participating in a clinical trial?

Talk to a Multiple Myeloma Research Foundation (MMRF) Patient Navigator to learn more, or use our clinical trials finder.

Emerging therapies

All drugs and therapies that have shown activity in multiple myeloma in laboratory studies must be studied in clinical trials before they are approved by the FDA for use in myeloma patients. Emerging therapies for multiple myeloma are in phase 1, 2, and/or 3 clinical trials. They can be drugs in the same class as existing FDA-approved drugs, or they can be in a new class.

Described below are the classes of multiple myeloma therapy that currently have drugs being tested in clinical trials.

Precision medicine

Increasingly, research into myeloma therapy is focusing on precision medicine—the treatment of each patient according to his or her specific or unique characteristics, such as myeloma genetic makeup and immune profile. The precision medicine approach, which uses molecularly targeted therapies (that is, drugs that specifically target errors in the genetic code [called mutations] in myeloma cells) better enables the patient and the health care team to choose the myeloma drug(s) that will be most effective.

The MMRF trial is evaluating drugs designed specifically for DNA mutations identified in myeloma patients. All of the drugs being investigated in MyDRUG have already been approved to treat other cancers, but they are not yet approved for patients with multiple myeloma. The results from MyDRUG will hopefully allow doctors to select treatments that are most likely to help patients achieve better treatment results (such as longer remissions).

Novel mechanisms of action

Many new and emerging therapies have novel mechanisms of action; that is, they work to kill myeloma cells in a way that differs from other categories of drugs. Drugs with novel mechanisms of action target certain proteins involved in cell growth and division. These drugs may target proteins that are specific to myeloma cells or all cells.

Drugs with novel mechanisms of action that are already approved include

  • Farydak (panobinostat) a histone deacetylase inhibitor
  • Xpovio (selinexor) a selective inhibitor of nuclear export

Immunomodulatory agents

Immunomodulatory agents are the mainstay of standard regimens used to treat multiple myeloma. They work by activating certain immune cells, preventing certain types of growth signals for cancer cells, and directly killing myeloma cells.

Immunomodulatory agents currently approved for use in patients with multiple myeloma include

  • Revlimid (lenalidomide)
  • Pomalyst (pomalidomide)
  • Thalomid (thalidomide)

Naked antibodies

Naked antibodies recognize and target a specific protein on the surface of myeloma cells, which enables them to help the patient’s immune system identify and eliminate the targeted myeloma cells.

Naked antibodies currently approved for use in patients with multiple myeloma include

  • Darzalex (daratumumab) and Sarclisa (isatuximab), which target and bind to a protein called CD38
  • Empliciti (elotuzumab), which targets and binds to a protein called SLAMF7 and can activate a particular group of cells of the immune system—the NK cells. These activated NK cells seek out and destroy myeloma cells.

Naked antibodies in clinical development include

  • CD38 as target
    • TAK-079
  • BCMA as target
    • SEA-BCMA
  • Other targets
    • BMS-986016
    • CJM112

Checkpoint inhibitors

A separate class of naked antibodies is called the checkpoint inhibitors. They work slightly differently than naked antibodies. Instead of simply flagging myeloma cells for destruction, checkpoint inhibitors release the hold that myeloma cells are able to put on a type of immune cell called T cells. Checkpoint inhibitors interfere with cell surface proteins that enable a myeloma cell to avoid the immune system; by blocking these proteins, the “brakes” on the immune system are released and the immune cells are able to kill myeloma cells. Checkpoint inhibitors have been used successfully in patients with solid tumors but are not approved for use in patients with multiple myeloma.

Emerging immunotherapies targeting B-cell maturation antigen (BCMA)

BCMA is a myeloma cell surface protein that is being used as a target for many different kinds of immunotherapies, because BCMA is found exclusively on myeloma cells.

Several types of BCMA-targeted immunotherapy are in clinical trials for patients with multiple myeloma.

Click here to learn more.

Antibody-drug conjugates

A type of antibody-based treatment—called antibody-drug conjugates (ADCs)—uses an antibody that is coupled to a cancer drug or a toxin. The antibody part of the conjugate binds to the myeloma cell—just as naked antibodies do—and the attached cancer drug or toxin kills the myeloma cell. Most of the antibodies in these agents target BCMA. This class of immunotherapy is not yet approved for use in patients with multiple myeloma.

Bispecific antibodies and bispecific T-cell engagers

Bispecific antibodies and bispecific T-cell engagers are forms of antibody-based immunotherapy in which two antibody fragments have been fused together: one fragment targets myeloma cells (making them easier for the immune system to find) and the other helps immune cells (by boosting their ability to find myeloma cells). Most of the agents in this class target BCMA on the myeloma cell and bind to a protein called CD3 that is found on the surface of T cells. This class of immunotherapy is not yet approved for use in patients with multiple myeloma.

CAR T therapy

Chimeric antigen receptor T-cell (CAR T) therapy involves collecting T cells from a patient’s blood and genetically reprogramming them so that they recognize and target a particular antigen on cancer cells. The reprogrammed CAR T cells are expanded by growing cells in a lab and are then infused back into the patient’s body, where they can attack and kill cancer cells.

CAR T therapies have recently been approved to treat some other cancers, but they are still being investigated in clinical trials for multiple myeloma. Results reported for these trials so far have been promising, with many patients with relapsed or refractory disease achieving long-term remission.

Experimental (Emerging) MM Therapies in Development*

Novel Agents: Phase 3 Precision Medicine: Venetoclax†, Phase 1,2 Precision Medicine: Abemaciclib†, Cobimetinib†, Dabrafenib, Enasidenib†, Erdafitinib†, Idasanutlin, Trametinib, Vemurafenib, Phase 3 Novel Mechanisms of Action: Melflufen, Phase 1, 2 Novel Mechanisms of Action: ·  CLR 131, Ibrutinib, INCB001158, INCB053914, Molibresib, ONC201, Pemigatinib, Ruxolitinib, Immunotherapies: Phase 3 Immuno-modulatory Agents: None, Phase 1, 2 Immuno-modulatory Agents: Iberdomide, TAK-573, Phase 3 Naked Antibodies: None, Phase 1, 2 Naked Antibodies: BMS-986016, CJM112, SEA-BCMA, TAK-079, Phase 3 Antibody-Drug Conjugates: Belantamab mafodotin, Phase 1, 2 Antibody-Drug Conjugates: CC-99712, FOR46, MEDI2228, STRO-001, Phase 3 Bispecific Antibodies and Bispecific T-Cell Engagers: None, Phase 1, 2 Bispecific Antibodies and Bispecific T-Cell Engagers: AMG 420, AMG 701, AMG 424, CC-93269, GBR 1342, JNJ-64007957, JNJ-64407564, PF-06863135, REGN5458, TNB-383B, Phase 3 CAR T-Cell Therapies: Idecabtagene vicleucel (ide-cel; bb2121), Phase 1, 2 CAR T-Cell Therapies: ALLO-715, bb21217, Descartes-08, Descartes-11, JCARH125, JNJ-68284528, NKR-2, P-BCMA-101, UCARTCS1A, Phase 3 Checkpoint Inhibitors: None, Phase 1, 2 Checkpoint Inhibitors: Abatacept, BMS-986207, Ipilimumab, Nivolumab, Pembrolizumab, TT-622

*Drugs listed are based on a search of with the following search parameters: multiple myeloma, United States, recruiting or not yet recruiting (last updated November 2019)

Being studied in the MyDRUG trial

* Being studied in the MyDRUG trial but currently on FDA hold