As a young girl growing up on a farm in Iowa, Deborah Stephens, DO, could not have fully imagined that one day she would be a physician scientist leading groundbreaking trials to improve care for cancer patients, particularly those with chronic lymphocytic leukemia (CLL) and lymphoma.
"I grew up on a farm and always worked with my grandpa, watching him deliver calves and giving vaccinations to cows. I was very excited about that," laughed Stephens. She is now Assistant Professor at the Huntsman Cancer Institute at the University of Utah, Director of the facility's CLL and Lymphoma Program, leader of a subspecialty clinic with a focus on treating patients with CLL and lymphoma, and the national principal investigator for the SWOG S1925 EVOLVE CLL Study, which is exploring early intervention with a targeted drug combination in patients with CLL. She might have been a veterinarian, but "...it's easier when the patients can tell you what's wrong with them," she quipped.
Stephens went to medical school at Kansas City University of Medicine and Biosciences, participated in internal medicine training at Cleveland Clinic, and then completed a hematology and oncology fellowship at The Ohio State University.
"When I originally went into medicine, I wanted to do primary care, but I became very interested in hematology and blood disorders during medical school. I rotated to the leukemia service at Cleveland Clinic, and there I realized I could deal with life-threatening blood disorders and cancers and work to cure people. I found I could develop a lifelong relationship with patients and, after their acute illness, establish their primary care management later," she explained.
Stephens noted she had a personal experience with CLL as well; an uncle fought the disease for many years "...and eventually died from a complication called Richter's transformation, which causes CLL to change into a more aggressive type of lymphoma. I became interested in CLL and, while at Ohio State, I was able to work in the clinic of John Byrd, MD, an internationally recognized expert in CLL. I said to myself, 'He's the kind of doctor I want to be-great with patients and excellent in the way he runs his research program.'"
One unique experience Stephens had while at Ohio State had involved the drug ibrutinib, "...which has been a major breakthrough and revolutionized the field of CLL," she told Oncology Times. "I was a trainee when the initial clinical trials were ongoing. Patients would come to see us in clinic and say, 'We've been told there's nothing else we can do. I'm going to die from my disease.' And then we put patients on this oral drug which was very well-tolerated and highly effective. These people, who essentially had been on hospice, went back to their regular lives. That experience made me drink the Kool-Aid for research. I saw what a big impact we can make in patients' lives by providing treatment that can reduce symptoms from their disease and prevent them from having to get a toxic therapy."
The Work at Hand
Stephens maintains a clinical practice and continues one-to-one relationships with patients. However, the lion's share of her time-about 70 percent-is spent in research where her efforts potentially can benefit millions.
"My primary interests include developing new targeted therapies for patients with CLL and lymphoma, studying resistance to current therapies, and developing supportive therapies for the complications of CLL," she explained. "It is important to understand, while survival of patients with CLL has really increased over the years, there's still no cure. So these people end up living with their diseases for many years, sometimes decades. One aspect of my work is always the search for the elusive cure of CLL. I think that will be accomplished through improvement or discovery of new therapies, with the focus on as limited toxicity as is possible."
Another of Stephens efforts explores Richter's transformation, that aforementioned switch when patients move into a more aggressive lymphoma disease state.
"The predicted survival of those patients is about 6-9 months; it's quite aggressive," detailed Stephens. "We are looking into such aspects as genetic background and the kinds of treatments we can do for these patients."
A third focus of Stephens' research work is an effort to determine if a more proactive early treatment course can benefit patients with CLL.
"CLL is unique in that patients without any symptoms can be diagnosed with this cancer. Those people usually are diagnosed when they've had a blood count done by their primary care doctor and the white blood cell count is way too high, or they just have an enlarged lymph node that is biopsied and reveals CLL," said Stephens.
It all comes as a shock to unsuspecting patients, particularly because they feel healthy. Suddenly they learn they have cancer, and no treatment will be done immediately.
"Because there is no cure, and because they don't have any symptoms, we recommend active observation or 'watch-and-wait.' Patients are diagnosed with cancer, [then] typically observed until the time when they develop symptoms or low blood counts from their disease. It can make patients very anxious. That's why we sometimes call it 'watch and worry,'" said Stephens.
"So I am chairing a clinical trial for early intervention with targeted therapies to see if we can prolong survival. We know the old toxic chemotherapies don't prolong survival if we give it early. But now we have new oral, less toxic, targeted agents-obinutuzumab and venetoclax-and we hope early intervention with a year of this therapy can prolong survival.
"I've developed a clinical trial and am international principal investigator on SWOG S1925 EVOLVE CLL study, which is a Phase III study comparing early intervention with that drug combination with delayed intervention with that combination. The clinical trial opened in December of 2020. At this point, we've enrolled five of our planned 247 patients. Our outcome is overall survival, so we're going to be following these patients for a long time. We've got a long way to go."
Other Research Projects
Yet another area which Stephens has embraced through her work is the improvement of quality of life.
"These patients still do have CLL, which suppresses their immune systems. And so they can get complications such as infections or secondary cancers. I'm really interested in, for example, how CLL patients respond to vaccines," she said.
Vaccine response is often pegged to where a patient is in their disease process and what prior therapy they've received. "Response definitely is not as good as the response of a person with an intact immune system," Stephens explained. "Of course, right now I'm looking at how people are responding to COVID vaccines. It's really widely variable for our patients. Many do not respond, so then the question is, 'What needs to be done to help prevent whatever infection we're trying to vaccinate against?'"
The physician scientist is also particularly interested in the occurrence of non-melanoma skin cancers, "...because they're very, very common and can actually be very aggressive in patients with CLL," she said. "I'm just getting ready to open up a large clinical trial, looking at an agent that might prevent skin cancer in these patients."
Asked why skin cancer occurs in them, Stephens answered, "I don't know, but that's one of the things I hope to find out with the correlative data associated with the clinical trial. My hypothesis is that it has to do with T-cell exhaustion. The immune system does not mount as good surveillance for a second cancer as for a primary cancer. I also think viruses are involved, which has made me particularly interested in studying the beta or cutaneous version of human papillomavirus."
Moving Forward
When not in clinic or her research lab, Stephens leads an active life-usually in tandem with her husband and their son, who is 4. Her life has changed a great deal since childhood days on that Iowa farm.
"There definitely were no mountains in my backyard in Iowa. There's a lot more to do here in Utah, especially during the winter, that's for sure," she said. "Here, we have great access to the outdoors. During the winter, we do a lot of skiing and snowshoeing. And during the summer, we do a lot of hiking or trail running and sometimes paddle boarding on the lake."
New to skiing when she moved to Utah ("...I could barely go down a green hill..."), Stephens said she now skis everything, including the advanced slopes. "And we are teaching my son how to ski already. I can say at 4, he probably skis as well, or maybe better, than I did at 30."
As life pushes forward, the researcher hopes to experience the satisfaction of success, just as she has in earlier work. She was an investigator on a clinical trial for a drug called acalabrutinib that is now FDA-approved for chronic lymphocytic leukemia.
"Research is certainly very, very rewarding, because we can help not only those immediately around us, but many people all across the world. It's so satisfying," Stephens said. "There have been huge improvements over the last decade, because we used to just have some non-specific, very toxic chemotherapy combinations. And now we have oral, significantly less toxic, targeted therapies. We're definitely moving in the right direction. But there still isn't a cure, so we're all still a little restless."
Valerie Neff Newitt is a contributing writer.