In the journey toward curing cancer, understanding why treatments sometimes stop working is just as important as developing them in the first place. A groundbreaking study from the University of Calgary is doing exactly that—shedding light on why many patients with multiple myeloma, the second most common blood cancer in adults, experience relapse after immunotherapy. The research, published in Nature Medicine, doesn't just document a problem; it's charting a path toward solutions that could transform how doctors approach this disease.
Multiple myeloma begins in the white blood cells responsible for creating antibodies. When myeloma cells multiply unchecked, healthy blood cells struggle to function properly. While effective treatments exist—including immunotherapies that can significantly extend survival—some patients eventually develop treatment resistance. The Calgary team, led by members of the Arnie Charbonneau Cancer Institute, set out to understand why.
"A treatment could be incredibly effective, bringing disease bulk down from about 100% to about 1% to 2%, but all it took was that one to two percent of the cells that were left to adapt and cause this relapse in patients," explains Dr. Holly Lee, MD, PhD, a clinical assistant professor at the Cumming School of Medicine and the study's first author. She collaborated with project leads Drs. Paola Neri and Nizar Bahlis, analyzing data from clinics across North America, Europe, and Asia.
The researchers focused on patients who had undergone bispecific T-cell engager therapy, which helps the immune system identify and attack myeloma cells by targeting a protein called GPRC5D on the tumor's surface. What they discovered was remarkable: the tumor cells adapted in multiple ways, with approximately 60%–70% of relapsed patients experiencing recurrence due to protein adaptation. Understanding these different escape routes is now guiding the development of next-generation treatments designed to anticipate and overcome these changes.
For Lee, this work represents a crucial step toward the ultimate goal: personalized cancer therapy tailored to each patient's unique biology. "Cancer is not one disease," she notes. "Each cancer and each patient behave very, very differently. We have patients who are in remission for four or five years and others who relapse within six months after receiving the same therapy."
The implications extend beyond multiple myeloma. The team emphasizes that these findings contribute to a broader understanding applicable to cancers across the board. Moving forward, the goal is to implement more targeted screening within clinical practices with faster turnaround times, supporting patients in real time as they navigate treatment. "For us to really cure myeloma, we have to understand the tumor cells and develop treatments to stay ahead of them building that resistance," says Lee. In Calgary, that understanding is already taking shape.