“Over the last 10 to 15 years, we have made tremendous advances in the treatment of multiple myeloma, which had limited treatment options in the ’90s. Overall, survival has doubled due to the introduction of new drugs,” says Hans C. Lee, MD, an assistant professor in the Department of Lymphoma/Myeloma at the University of Texas MD Anderson Cancer Center in Houston. New classes of cancer drugs, including immunotherapy drugs and monoclonal antibodies, have changed the outlook for many people with this disease.
People with relapsed (comes back after treatment) or refractory (doesn’t respond to the first-line treatment) multiple myeloma are still a challenge to treat even with new options, and their disease tends to be more aggressive, says Lee. “But for patients with standard-risk multiple myeloma, that’s where we have made substantial progress.”
New Multiple Myeloma Drugs
Several new drugs have been approved to treat multiple myeloma since 2015, including relapsed and refractory forms of the disease, says Lee.
Belantamab mafodotin-blmf (Blenrep) is the first in a new class of drugs called antibody drug conjugates (ADC). It is used to treat patients who have been already treated with at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. Bienrep targets the protein BCMA (B-cell maturation antigen) which is the protein protecting the cancer cell.
Daratumumab (Darzalex) is another monoclonal antibody. You can take it either alone or combined with dexamethasone and either lenalidomide or bortezomib (Velcade). Daratumumab targets a protein on the surface of myeloma cells called CD38. It seeks out the protein and then kills the cancer cells it’s attached to.
Elotuzumab (Empliciti) is a type of drug known as a monoclonal antibody. It revs up your own immune system to help you fight the cancer. It seeks out a molecule on cancer cells called SLAMF7. It’s combined with other myeloma drugs: either with lenalidomide (Revlimid) and dexamethasone or with dexamethasone and a newer drug called pomalidomide. It's effective in people with more aggressive forms of myeloma.
Isatuximab (Sarclissa) is also a monoclonal antibody which works similar to daratumumab. It is used in combination with pomalidomide and dexamethasone and is for those who have tried at least two other therapies. It, too, targets CD38 and slows the growth of cancer.
Ixazomib (Ninlaro) is the first and only oral proteasome inhibitor that the FDA has approved for multiple myeloma treatment. Proteasomes are enzyme complexes that help cancer cells recycle proteins they need to grow. Ixazomib blocks proteasomes to kill myeloma cells. It's combined with lenalidomide and dexamethasone. It's used in people who’ve tried at least one other myeloma treatment.
Melphalan flufenamide (Pepaxto) is administered through a monthly IV to patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy. It targets the myeloma cell itself, killing it. It is the first anticancer peptide-drug conjugate approved in multiple myeloma.
Panobinostat (Farydak) is the first of a class of drugs called histone deacetylase (HDAC) inhibitors to be approved to treat multiple myeloma. It’s combined with bortezomib and dexamethasone. HDAC inhibitors kill myeloma cells by stopping them from making a certain protein that drives fast cell growth. It’s used in people whose myeloma has not responded to at least two standard treatments.
Selinexor (Xpovio) is a new type of multiple myeloma drug called a selective inhibitor of nuclear export (SINE). The FDA approved it for treatment of relapsed or refractory disease in July 2019. It’s combined with dexamethasone and is used to treat people who've tried at least four previous therapies. It works by blocking XPO1, a protein that allows cancer cells to thrive.
What’s on the Horizon?
Three potential breakthroughs in multiple myeloma therapy are still in the test phase, but they seem very promising, Lee says.
Antibody-drug conjugates (ADCs) combine a monoclonal antibody and chemotherapy in one drug. One ADC in development now, belantamab, has a monoclonal antibody that seeks out a protein on the surfaces of myeloma cells called BCMA. Once it finds its target, it delivers chemotherapy directly to the cancer cells, says Lee.
T-cell engagers are two-armed antibodies that fight cancer cells in two separate ways: They look for BCMA and T cells, which are part of your own immune system, he says. “One arm of the antibody targets BCMA on the myeloma cell’s surface. The other arm seeks out a protein called CD3 on T cells. Basically, it’s the kiss of death for the cancer cells. The T cell is activated, comes into contact with the myeloma cell and kills it.” These drugs are also called bispecific T-cell engager antibodies, or BiTEs.
CAR T-cell therapy has been a successful treatment in another blood cancer, lymphoma, so now doctors are studying whether it can work in myeloma, says Lee. “It genetically engineers T cells to identify, attack, and kill myeloma cells.” CAR T-cell therapies like BB2121 have shown high response rates even in relapsed or refractory multiple myeloma patients, although it’s not a cure, he says.
Another positive step for multiple myeloma treatment is the advance in genomic medicine, says Lee. Doctors are able to do a biopsy, or tissue sample, and see gene-related information about your cancer more quickly and cheaply than in the past. “Hopefully, soon we will be able to use this data in real time, maybe to help us find the optimal way to sequence your therapies, or even to individualize treatment.”