By: Keri Sweetman
In 2007, when Dr. Mona Shafey was a first-year hematology resident in Ottawa, she watched her instructor tell a cancer patient that he was in complete remission after his treatment. He was so happy he bear-hugged the physician right off her feet.
It was in that moment that Shafey knew she wanted to work with cancer patients. “Observing the patient’s reaction to that news, I said, ‘I want to be able to do that.’”
That image has stayed in her mind for 16 years. Now, Shafey is living in Calgary and doing all she can to offer hope to patients with lymphoma, leukemia and other blood cancers. She works directly with patients as a malignant hematologist and as an investigator in a growing number of clinical trials, mainly at the Tom Baker Cancer Centre and largely involving groundbreaking cellular therapy. And she believes the future of treatment for many blood cancers, and possibly other malignancies, will involve CAR T-cell therapy.
Shafey completed her medical degree and residencies (internal medicine and hematology) in her hometown at the University of Ottawa, graduating in 2008. She was then accepted as a fellow in the University of Calgary’s highly regarded cellular therapy program, which she was drawn to because of its innovative approaches to using cellular therapies for patients with blood cancers. She completed her fellowship training and started a university staff position in Calgary in July 2010.
Since October 2022, Shafey has been the clinical director of the Alberta Cellular Therapy and Immune Oncology Initiative (ACTION). This ambitious program supports the development of next-generation therapies for children and adults using a patient’s own immune system to fight cancer. One of the most promising therapies involves engineering CAR T cells (chimeric antigen receptor T cells, which are genetically modified immune cells from the patient) to find and attack cancer cells. This therapy, which was developed more than 10 years ago, has been most successful in patients diagnosed with blood cancers who have not responded to traditional treatment such as chemotherapy or stem cell transplant. In the past, most of those patients would die within six months of a cancer recurrence.
Shafey has been the principal investigator for 12 clinical trials, six of which are currently ongoing. She is collaborating on another 15 active trials; her own patients are enrolled in five. Most of the trials have involved new approaches to treating lymphoma, including CAR T-cell therapy and stem cell transplants. Some of the trials have received funding from the Alberta Cancer Foundation, including a current project she is leading that is investigating the use of GCAR1, a CAR T-cell product developed at the University of Calgary, for a patient with alveolar soft part sarcoma (ASPS). Shafey’s team also recently received nearly $3 million in funding from the Canadian Institutes of Health Research for a multi-centre phase 1 clinical trial investigating the safety and efficacy of using GCAR1 in patients with ASPS and some types of kidney and breast cancers.
“Alberta Cancer Foundation has consistently supported the early work of investigators who have ideas to support Albertans who need treatments that may not necessarily be interesting or attractive enough for a pharmaceutical company to get involved,” says Shafey. “That early support is really key.”
Also on the list of Shafey’s achievements is being the director of the Alberta Blood and Marrow Transplant Program, a role she’s held since 2019, which oversees cellular therapy in the province. Cellular therapy refers to any treatment involving collected cells, including stem cell transplants (either from donors or patients’ own stem cells), lymphocyte infusions, CAR T-cell treatment, and therapies for non-cancer patients with autoimmune diseases and blood disorders.
The bulk of what the program does now is stem cell transplants, says Shafey, “but the greatest area of growth over the next three to five years is in CAR T cells.”
Health Canada approved CAR T-cell products in 2019 for patients with certain types of leukemia and lymphoma, but the treatment was initially only offered in Ontario and Quebec. There was no CAR T-cell program in Alberta until August 2020, when the province and the Alberta Cancer Foundation announced $15 million in funding to start offering the therapy here. Of that, $5 million from Alberta Cancer Foundation supports an Edmonton team, led by Dr. Michael Chu, that’s developing made-in-Alberta CAR T-cell products. The remaining $10 million pays for a provincial initiative to provide CAR T-cell therapy to adult and paediatric patients with aggressive lymphoma, or B-cell acute lymphoblastic leukemia, who have had a recurrence or have not responded to treatment.
The Calgary team started offering CAR T-cell treatments in January 2021, says Shafey, who oversees the adult portion of the program. Of the first 26 patients, 84 per cent had a complete or partial response to the treatment. After one year, 50 per cent of those patients who received the CAR T-cell therapy were alive and in remission, which was higher than expected. There were also fewer toxicities and side-effects than expected.
“It’s hard to predict, when you have a patient in front of you, if they’re going to be someone who does really well or if they will be a person who doesn’t respond at all. I like to prepare them for all possibilities, but we always hope for the best.”
Dr. Carolyn Owen, an associate professor of medicine and oncology at the University of Calgary, has known Shafey for 20 years — they were both in the University of Ottawa’s faculty of medicine. They share many of the same clinical interests and often work together on clinical trials.
Shafey’s strengths include her “broad knowledge base and her ability to develop good relationships with patients, to be able to explain the implications of clinical trials in layman’s terms, while still understanding and advocating for the scientific benefits,” says Owen.
She considers Shafey’s four years leading the Alberta Blood and Marrow Transplant Program as highly successful. Shafey became the director at a really critical time, with the new cellular therapies becoming available. “She took over at a time of great change, and I think she’s done an excellent job leading that change, but also trying to overcome a lot of logistical obstacles — and there were many,” says Owen.
Three CAR T-cell products have been approved and funded in Alberta, with two more expected to receive the green light next year. So far, these products have been used only as a third-line treatment for aggressive lymphoma and B-cell acute lymphoblastic leukemia, meaning they are given to patients with no other viable treatment options. But Shafey expects the products to be available as a second-line treatment (after the first relapse) for high-risk patients with aggressive lymphoma as early as 2024. She also hopes the therapy will be available for multiple myeloma patients in Alberta next year.
Shafey hopes CAR T-cell therapy will be the standard of care for many cancers in the future.
“There’s a lot of promise in the hematological malignancy world. We’ve already seen that. We’re going to see where this expands — to new types of tumours, but also for earlier stages of disease,” says Shafey.
It’s an exciting time to be involved in this groundbreaking research and treatment, particularly in her specialty area.
“For blood cancers, particularly B-cell malignancies, there is an explosion of CAR T-cell therapies that are going to keep us busy for many years to come,” she says.
Three Questions With Dr. Mona Shafey
Q: What’s the biggest misconception about what you do?
That lymphoma is a single disease. When somebody’s diagnosed with lymphoma, it’s very important to know what type of lymphoma they have because the treatment and prognosis are completely different.
Q: What motivates you?
My patients. Even if a patient can’t be cured, being able to offer treatments that can improve their quality of life means I can still have a positive impact on them.
Q: Why does your research matter?
We as clinicians always want to do better and sometimes the only way you can do that is through a research study. That’s how I convince many of my patients to consider clinical research, because some of the best therapies are on these trials.