Identifying Patients at Risk of Multiple Myeloma Relapse Can Improve Treatment Plans
Multiple myeloma remains an incurable blood cancer, but advances in therapy, including immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy, have dramatically improved outcomes for many patients. Still, a meaningful proportion experience relapse, sometimes early after treatment. Understanding why remains an urgent scientific and clinical priority.
This challenge is the focus of research presented at the American Society of Hematology (ASH) annual meeting by Doris Hansen, MD, an oncologist in Moffitt Cancer Center’s Blood and Marrow Transplant and Cellular Immunotherapy Department.
“We need to continue to improve outcomes for our patients and forge a path toward a cure,” Hansen said. “A critical step is identifying which individuals are at risk for early relapse, particularly those who relapse within 18 months of CAR T-cell therapy, so we can tailor treatment strategies accordingly.”
A Multicancer Center Study Hopes To Predict Relapse
Hansen is leading a multicenter study to identify clinical and biologic features that predict early relapse after CAR T-cell therapy. Traditional definitions of high-risk multiple myeloma rely on chromosomal and molecular abnormalities, but these criteria do not capture all patients with aggressive disease biology.
“The current staging systems do not fully identify every high-risk patient,” Hansen said. “Functional high-risk patients may not show baseline high-risk features yet still relapse early. Recognizing and managing functional high-risk disease remains a major unmet need.”
Some patients may need intensified treatment approaches, such as consolidation, maintenance or more aggressive bridging therapy before CAR T to optimize long-term efficacy and safety outcomes, Hansen says.
The Importance of Bridging Therapy
CAR T-cell therapy is a type of immunotherapy that uses a patient’s own immune system to find and destroy cancerous cells. It involves genetically modifying T cells — a type of white blood cell — to recognize proteins on the surface of cancerous cells and destroy them.
Bridging therapy refers to the treatment patients receive while waiting for their genetically modified CAR T cells to be manufactured and returned. The goal, Hansen says, is to reduce disease burden before the CAR T cells are infused.
“This is recommended for nearly all patients,” Hansen said. “Lower disease burden at the time of CAR T infusion is associated with better outcomes and a lower risk of immune toxicities.”
Relapse in multiple myeloma can appear as rising myeloma protein markers in the blood or as new bone or soft tissue lesions on imaging.
“If we can detect high-risk features early, we can design tailored clinical trials that intensify treatment for those who need it most and avoid overtreatment in those who don’t. By identifying early relapse predictors, we can enhance the long term efficacy of these novel immunotherapies and meaningfully improve survival, disease control and quality of life for our patients,” Hansen said.
Moffitt has played a central role in developing this risk-stratification framework. The findings presented at ASH represent one of the largest and most detailed analyses to date of early relapse after commercial ciltacabtagene autoleucel, a U.S. Food and Drug Administration-approved CAR T treatment for multiple myeloma.
