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Research Highlight | May 09, 2023

Pan-Canadian multiple myeloma study recruits 95 patients, finds those resistant to immunotherapy show T-cell exhaustion signatures

In 2022, an estimated 4,000 Canadians were diagnosed with multiple myeloma – an incurable cancer that affects the blood and bone marrow. And while this is a heterogeneous disease with variations in each case, patients suffering from myeloma are currently monitored and treated the same.

To better understand how existing multiple myeloma treatments work and to develop more effective ones, Dr. Tony Reiman is leading the Multiple Myeloma Molecular Monitoring (M4) cohort study, funded by TFRI since 2017.

“Our team includes leading myeloma researchers at various institutions across the country. We've got clinicians enrolling patients at cancer centres from coast to coast in the cohort, and we've got researchers at several labs across the country working with samples,” says Dr. Reiman, a medical oncologist and professor at the University of New Brunswick.

To characterize and monitor multiple myeloma in the blood and bone marrow, participating centres have been working to assemble a prospective cohort, with 95 of 100 patients enrolled.

“It’s taken some time to get to the point where we’re starting to see the fruits of our labour,” says Dr. Reiman says, referring to unexpected delays due to COVID-19, “but we’re starting to see them now and are expecting first papers this year.”

One such development is the recent publication of a study in the journal Cancer Cell, led by Dr. Nizar Bahlis, an associate professor of medicine at the University of Calgary and an M4 project principal investigator. Using T-cell receptor sequencing, Dr. Bahlis and his team are exploring mechanisms of immunotherapy resistance in patients with multiple myeloma.

“The team has been profiling bone marrow T-cells in multiple myeloma patients, comparing the T-cell profiles of those who respond to T-cell engager therapies with those who don’t,” explains Dr. Reiman. Perhaps more importantly, he continues, they’re finding signatures of T-cell exhaustion in patients who aren’t responding to therapy, whereas those who are responding appear to have a more active and robust T-cell population.

“It’s fascinating to see the varied mechanisms of innate and sort of acquired resistance to these novel myeloma therapies,” he says. “This is of great interest to the myeloma community and suggests avenues for potentially circumventing resistance in the future.”

As the leader of TFRI’s first pan-Canadian study led from New Brunswick, Dr. Reiman is working closely with the various sites, including those in Vancouver, Calgary, Toronto and Montreal. His hope is that the research coming out of this collaborative study will not only improve multiple myeloma treatments in Canada, but also contribute to the development of cancer research infrastructure on the East Coast.

“Here in Atlantic Canada, we don't have the cancer research that exists in places like Toronto, Vancouver and Montreal, but we've been building from the ground up,” he says. “The opportunity provided by funding from the Terry Fox Research Institute to do this work in Atlantic Canada is helping us grow our capacity and give Atlantic Canadian patients, students and people the opportunity to get involved in this work and make a meaningful contribution.”


The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients


Mirco J Friedrich, Paola Neri, Niklas Kehl, Julius Michel, Simon Steiger, Michael Kilian, Noémie Leblay, Ranjan Maity, Roman Sankowski, Holly Lee, Elie Barakat, Sungwoo Ahn, Niels Weinhold, Karsten Rippe 8, Lukas Bunse, Michael Platten, Hartmut Goldschmidt, Carsten Müller-Tidow, Marc-Steffen Raab, Nizar J Bahlis


This study was partially funded by a Terry Fox Translational Research Program in Multiple Myeloma Molecular Monitoring (M4) Study.