WRNMMC, Bethesda, Md.  –   “We need to temper our excitement over recent advances with humility and resolve, as the battle is still far from being won,” stated Dr. Clifton Mo in discussing multiple myeloma (MM).

Director of Autologous Stem Cell Transplantation for Multiple Myeloma and associate director for the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute, Mo was the guest speaker during the John P. Murtha Cancer Center’s (MCC) annual Multiple Myeloma Lecture at Walter Reed on Oct. 27. The MCC is the Department of Defense’s only Cancer Center of Excellence.

The annual lecture is named for Michael Sheehan, the former assistant secretary of defense for special operations and low-intensity conflict during the Obama administration, and coordinator for counterterrorism during the Clinton administration. He was also a distinguished chair at West Point and a terrorist analyst for NBC News.

Sheehan, a patient of Mo when the latter was on staff at Walter Reed, died from MM on July 30, 2018, at age 63.

“There are miles to go before we sleep,” said Mo, sharing the title of his lecture and the battle against MM, which is cancer of plasma cells (the white blood cells that make antibodies for protection against infections).
“In myeloma, the cells grow too much, crowding out normal cells in the bone marrow that make red blood cells, platelets, and other white blood cells,” according to the Centers for Disease Control and Prevention (CDC).

Initially, those with MM may show no symptoms, but as the disease progresses, it may manifest itself in bone pain, anemia, kidney dysfunction, and infections.

It’s not known what causes MM, but risk factors include obesity, radiation exposure, family history, age, and certain chemicals. According to the CDC, World Health Organization (WHO), and National Cancer Institute (NCI), MM occurs most commonly in people over 60, and the average age at diagnosis is 70. The disease also occurs twice as frequently in Black people than in White people, and it appears to also be more common in the Middle East, North Africa, and the Mediterranean. Also, people who have been exposed to radiation or asbestos, benzene, pesticides, and certain other chemicals, as well as those exposed to wood products, such as carpenters, furniture makers, and paper makers, may be at higher risk for development. There is also a high incidence of MM among firefighters, those in agricultural and industrial occupations, and those exposed to herbicides, including Agent Orange. MM is also slightly more common in men.

“The deluge of advancements [in MM therapy] are going to continue as opposed to stop over the next few years. Ultimately, this has been a great thing, and prognosis has improved remarkably and will continue to improve dramatically for our patients,” said Mo, who was a hematologic oncologist and transplant specialist at Walter Reed before assuming his current positions at the Dana-Farber Cancer institute.

He completed his internal medicine residency training at Walter Reed Army Medical Center (WRAMC) in 2007 and his hematology/oncology fellowship training at the National Capital Consortium (WRAMC/National Naval Medical Center) in 2010. A West Point and Yale School of Medicine graduate, Mo spent 15 years as an active-duty physician and officer in the U.S. Army, achieving the rank of lieutenant colonel. In 2010, he deployed to Iraq for Operation New Dawn where he served as a front-line medic, treating service members and others.

At Dana-Farber’s Jerome Lipper Multiple Myeloma Center, Mo’s duties include refining the transplant’s role for MM patients to improve their standard of care and quality of life.

He explained that in 2006, MM patients began being treated with novel agents. “They were doing better on average than before these drugs were available,” he shared.

“In 2010, the combined novel agent era of myeloma began to become the de facto standard of care in the United States,” said Mo. “This was due in large part to pre-clinical work,” he added. Most drug therapies employ multiple agents, or triplet or quadruplet therapies, he explained.

He said the decision for transplant should be “individualized.”

“Treatment approach will become increasingly individualized until a cure is reached,” Mo stated. “Even then, it will not be uniform owing to heterogenous disease biology and patient factors,” he added.

“T-cell redirection therapy is probably the biggest news over the past couple of years,” Mo said. The therapy using chimeric antigen receptor (CAR) T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), leading to the approval of 2 CAR T-cell products and numerous BiAb trials, according to the National Institutes of Health.
T-cell therapy is designed to unleash the immune system against cancer cells to eradicate the cancer using the patient’s own immune cells, or T-cells.

Why can’t we cure MM already? Mo said it could be one, or a combination of the following reasons: “unparalleled survivability of the plasma cell; drastically altered and protective immune microenvironment; inability to get at the center stem cell with current immunotherapy target; are the current classes of drugs just not potent enough; or do we need to come at this from an entirely different [way].”