This article was written by Raymond Thertulien, MD, PhD, System Director, Multiple Myeloma & Plasma Cell Disorders for the Novant Health Cancer Institute.

In honor of Multiple Myeloma Awareness Month this March, we want to celebrate the courage of multiple myeloma patients and their caregivers while increasing awareness of the disease. This month isn’t just about awareness – it’s also about reiterating how important it is to fund more research to work toward a cure.

Multiple myeloma is a blood disorder, a disease of the immune system that involves abnormal proliferation of plasma cells, which are the cells responsible for making antibodies to protect us against infections. For people who suffer from this cancer, their immune system is compromised; that puts them at risk for infection. This disease also causes anemia, kidney failure and bone disease, which can lead to fractures and high calcium in the blood. It can also cause symptoms such as muscle, heart, and nerve problems, as well as constitutional symptoms (fatigue, drowsiness among others).

The American Cancer Society estimates that 35,780 people in the U.S. will be diagnosed with multiple myeloma in 2024, including 1,370 in North Carolina. About 12,540 deaths are expected in the country with 470 deaths in N.C.

The incidence of multiple myeloma is more than twice as common in Blacks as in whites. After Blacks come Native Americans and Alaskan Natives, Hispanics and non-Hispanic whites. The incidence is lowest in Asian and Pacific Islanders. The death rate for Black people is twice as high as it is for whites.

Although the incidence of multiple myeloma has been increasing, the death rate, fortunately, has not shown the same trend. The overall survival of patients diagnosed with multiple myeloma has improved significantly in the past five to 10 years. The five-year relative survival rate for multiple myeloma patients diagnosed between 2011 and 2017 and followed through 2018 is 56%. (It was 49% for the years 2005-2011 and only 27% from 1987-1989.)

This progress is attributed to development of new drugs and regimens to treat the disease, including adoption of autologous stem cell transplantation as standard of care.

Thalidomide was introduced in the late 1990s as an effective drug for the treatment of multiple myeloma. It was the first in a class of agents called immunomodulatory drugs (IMiD); it is now rarely used in the U.S. It has mainly been replaced by other derivatives such as Revlimid (lenalidomide, approved in 2005) and Pomalyst (pomalidomide, 2013). More potent agents in that class are in development; they are named Cereblon E3 ligase modulators (celmods).

Proteasome inhibitors (PI) are another class of drugs introduced in early 2000s that revolutionized the way we treat multiple myeloma. Velcade (bortezomib) was introduced in 2003. Kyprolis (carfilzomib), another proteasome inhibitor, was approved in 2012. Ninlaro (ixazomib), an oral PI was approved in 2015, a very important year for multiple myeloma, as five new agents/regimens were approved that year for treatment.

Soon after the introduction of these agents, the combination of these new drugs in doublets and later in triplets with steroids started to demonstrate significant improvement in response and survival.

New class of agents introduced in 2015 included Farydak (panobinostat), histone deacetylase inhibitor and monoclonal antibodies. Monoclonal antibodies (Darzalex (daratumumab), Sarclisa (isatuximab) and Empliciti (elotuzumab) recognize receptors (CD38, SLAMF7) on the plasma cells that lead to killing of those cells by various mechanisms.Antibody drug conjugates were developed by attaching chemo drugs to such monoclonal antibodies to deliver chemo directly to the plasma cells like “smart bombs”.

Xpovio (selinexor), yet another drug approved in 2019, has a completely different mechanism of action. It prevents the cells from getting rid of toxic substances inside them, which leads to their death.

More recently chimeric antigen receptor (CAR) T cells and biallelic T cell engagers (Bites), otherwise known as bispecific antibodies, were introduced in the toolbox of multiple myeloma treatments we have available. They are not yet widely adopted because of their potential toxicities. They are only available at major cancer centers such Novant Health Cancer Institute where we have the expertise to manage these new toxicities. However, these drugs are very effective and are already changing the way we treat multiple myeloma.

For the treatment of multiple myeloma, a combination of drugs is better than single agents; the combination of drugs with different mechanisms of action is effective even in cases where the single agents by themselves may not be completely active. Thus, drug combinations can help overcome resistance. As always, when living in abundance, we need to learn not to waste. In the case of multiple myeloma, we need to use our bounty when it benefits patients best. That is a learning process, because we do not yet have clinical trial data to guide us on the correct sequence of treatment regimens. Until then, it is best to seek the experience of a multiple myeloma physician.

Multiple myeloma is becoming more and more a chronic disease. Treating multiple myeloma has been a success story to build on. We, at Novant Health Cancer Institute, are building a world-class multiple myeloma program with clinical research at the forefront to continue developing new multiple myeloma treatments as we seek a cure.