Oct. 20, 2023
UCalgary and AHS researchers discover how multiple myeloma cells become resistant to immunotherapy
Calgary, AB – Lisa Mack is cancer-free, for now, and looking forward to her 75th birthday in December. She was a participant in a clinical trial at the Tom Baker Cancer Centre (TBCC) that has helped University of Calgary and Alberta Health Services researchers better understand why multiple myeloma (MM) cells become resistant to immunotherapy.
“Despite promising results obtained by using novel immunotherapeutic approaches, every multiple myeloma patient relapses at some point. We wanted to understand why this happens in order to prevent disease relapse and develop better treatments for our patients.”
Dr. Nizar Bahlis, MD, associate professor, Cumming School of Medicine, senior author on the paper
The scientists obtained tumour samples from Mack and 29 other patients who were treated with chimeric antigen receptor T cell (CAR T) therapy and/or bispecific T cell engagers. Researchers separated the myeloma cells and subjected them to single cell sequencing to understand how these cells become resistant to these therapies. These immunotherapies go after two targets expressed on malignant plasma cell surface: B cell maturation antigen (BCMA) and G-protein coupled receptor family C group 5 member D (GPRC5D).
“We found that the tumour cells escape the reach of immunotherapy by losing or changing these targets (BCMA, GPRC5D) on their surface. When this happens, the tumour becomes invisible to the targeted therapy, like a strong signal that suddenly disappears from a radar screen.”
Dr. Holly Lee, MD, hematologist, PhD student, first author on the paper
Dr. Paola Neri, MD, PhD, oncologist TBCC, Alberta Health Services and co-senior author on the paper, says the study revealed new understandings of MM cell behaviour that have never been documented.
“We have noticed that the tumour can also change and mutate, altering the target recognized by these therapies, making the tumour cells unrecognizable to the therapies. Therefore, screening for these changes is key. If you know that the tumour mutations are present you can consider different targets or other therapeutic options, personalizing the treatment for our myeloma patients.”
Dr. Paola Neri, MD, PhD, oncologist, Alberta Health Services, co-senior author on the paper
Single cell sequencing is not a routine procedure for myeloma patients. Neri says the next step will be to develop a test that could be used to screen for these mutations and help guide therapy selection.
“Our results suggest the importance of periodically profiling myeloma cells throughout a patient’s treatment course, ideally every three months. This proactive approach would enable us to adapt the treatment strategy in response to any tumour mutations that may arise,” says Bahlis. “As more immunotherapies are being developed it is critical to understand which ones will work the best and in which scenario.”
“Multiple myeloma is a very difficult cancer to treat. I’ve been cancer-free before, but it always comes back,” says Mack. “I was diagnosed 15-years ago and have undergone a lot of treatments including stem cell transplants and chemotherapy. I’m very grateful for my faith, the opportunity to participate in this clinical trial, and the research team.”
The Bahlis lab led this research and collaborated with investigators in Germany and the United States. Findings are published in Nature Medicine.
"The team, led by clinician-scientists Drs. Nizar Bahlis and Paola Neri, are truly leading the field nationally and internationally,” says Charbonneau Cancer Institute Director, Dr. Jennifer Chan, MD, who highlighted that the team has now published five important papers on precision cancer medicine in the last seven months. “These publications show what can be achieved when every research question drives toward clinical impact – and what can be achieved when bright minds, patients, patient samples, advanced technologies, and rigorous science come together.”
The Bahlis lab is supported primarily through philanthropy and research grants obtained from national and international societies such as the Terry Fox Foundation, Myeloma Canada, Alberta Cancer Foundation, Leukemia Lymphoma Society of Canada, International Myeloma Society, the Paula and Rodger Riney Multiple Myeloma Research Program Fund, and the Multiple Myeloma Research Foundation (MMRF).
Media Inquiries
Kelly Johnston
Sr. Communications Specialist, Media Relations
Cumming School of Medicine, University of Calgary
Kelly.johnston2@ucalgary.ca
403-617-8691
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About Alberta Health Services
Alberta Health Services is the provincial health authority responsible for planning and delivering health supports and services for more than four million adults and children living in Alberta. Our mission is to provide a patient-focused, quality health system that is accessible and sustainable for all Albertans. Our current focus is on reducing emergency department wait-times, improving EMS response times, increasing access to surgeries, and improving patient flow.
The Arnie Charbonneau Cancer Institute
The Arnie Charbonneau Cancer Institute is a community of researchers and educators dedicated to a cancer-free future. Charbonneau is meeting the cancer challenge through discovery and innovation in basic and applied research. The Institute brings together scientists and physicians to integrate research and care across disciplines – from understanding and preventing cancer, to transforming its detection and treatment, to improving life with and after cancer. Our members include researchers at the Tom Baker Cancer Centre and the University of Calgary’s Cumming School of Medicine and Teaching Hospitals. To learn more about Charbonneau, visit charbonneau.ucalgary.ca/