Tracing the Story of Myeloma

MULTIPLE MYELOMA isn't defined by its speed.

This cancer of plasma cells, which makes up less than 2 percent of all new cancer cases, unfurls slowly. It begins with mutations that produce abnormal white blood cells in bone marrow. The process often halts there, and those warped cells remain a minority.

But for 20 percent of patients, cancer steadily crowds out healthy cells. Here, oncologists apply an evocative label: smoldering multiple myeloma. For an unfortunate minority, their grim trajectory ends with cancer hijacking marrow, causing painful lesions that result in bone fractures.

So, if we know the plot, how can researchers halt the narrative?

Indiana University School of Medicine has a tool to help them sketch an outline for each patient: the Indiana Myeloma Registry. Launched in 2018, the registry has steadily amassed a repository of tissue samples, along with a rich trove of medical backgrounds and treatment histories. Soon, it will reach a pivotal milestone: a statewide enrollment of 1,000 patients.

"It is our mechanism for writing the history of each patient," said Mohammed Abu Zaid, MD, who helped launch the registry at the IU Melvin and Bren Simon Comprehensive Cancer Center before moving on to NYU Langone Health.

Biobanks aren't a revolutionary concept. Yet IU's registry—funded through the university's Grand Challenges program—wanted to go beyond physical samples. Rapid advances in therapy mean myeloma patients are living longer, and some researchers envision a future where treatments more closely resemble those for a chronic condition.

That progress makes it vital to follow patients over a prolonged period and trace the progression of their disease. That outlook–and the data required– make IU's registry distinct. Along the way, the setup should help clear another persistent hurdle in cancer research: lack of diversity.

Each patient in the registry supplies a saliva sample, which can be done remotely through a mailed kit, along with their medical history. Researchers use the physical sample to generate a genetic profile.

The sample also allows Brian Walker, PhD, a medical and molecular genetics professor, to deploy next generation sequencing to uncover the mechanics that slowly drive myeloma. Cells used in this research typically come from patients with highly aggressive cancer. Using the registry offers Walker's lab the opportunity to explore whether mutations vary based on severity.

Recently, the lab showed that some of these white blood cells lack a gene that acts as a copy editor, preventing transcription errors or misplaced bits of genomic code. As precursor conditions trudge toward full-blown cancer, those mistakes pile up.

A patient's medical history, age, and demographics are another set of variables the lab can use to distinguish how cancer behaves. It's a level of granular detail that's often lacking. "You're not inferring relationships," said Walker, the Daniel and Lori Efroymson Professor of Oncology. "You can see exactly what the changes are, how the cells behave, and what the biology is."

Eventually, researchers could find pressing answers to vexing questions. Why do only one percent of patients with precursor conditions progress to myeloma? If we understood those mechanics, could we prevent the cancer?

"If nothing else, understanding those genetic differences would let us create subtypes and stratify patients more effectively," said Kelvin Lee, MD, director of the IU Simon Comprehensive Cancer Center, H.H. Gregg Professor of Oncology, and a myeloma researcher.

When patients enroll in IU's registry, they consent to provide occasional blood and bone marrow samples and access to their medical records. Those tissue samples, which are stored in Indianapolis, serve as time-series events. Paired with a treatment history, the registry crafts a real-time account of how myeloma behaves.

Researchers can learn how people respond to therapy, what changes are happening in cancer cells, and why some don't respond. "Even now, we are able to provide better tools to determine their prognosis," said Rafat Abonour, MD, the Harry and Edith Gladstein Professor of Cancer Research.

Those insights are coming at a crucial moment.