Similar data-driven methods are used to address the challenges faced by cancer patients experiencing depression. Hernandez-Boussard and her team have been studying depression after a cancer diagnosis. By applying machine learning, a branch of artificial intelligence (AI) that uses algorithms and statistical models to make data-based predictions, they have identified features associated with depression in these patients. One significant finding was the association between loneliness and depression following a cancer diagnosis. “If we can identify recent losses in a patient’s life, like a divorce or the death of a loved one, we can better predict and manage their risk of depression,” explains Hernandez-Boussard. 

Integrating data from a variety of sources, her team crafts comprehensive profiles of patients. This holistic approach allows for targeted interventions that address not only the clinical symptoms of depression but also the social and emotional factors at play. For example, if a patient is flagged for significant loneliness following a divorce, the healthcare team can proactively connect them with support groups, counseling services, or community resources. This not only helps to mitigate their risk of depression but fosters a more supportive and responsive care environment.

“The advances in this field over the last 10 years have been truly mind-blowing,” says Fakhri. “Seeing the success of these drugs, and just how dynamic the field has been, made me want to keep working on CLL.”

Broad Clinical Trial Options

In 2022, Fakhri became the director of the CLL clinical trial portfolio at Stanford after the passing of Steven Coutre, MD, who had established the clinical research program in the Division of Hematology. Since joining, she has launched five new clinical trials for patients with CLL. She is also hard at work to open clinical trials benefiting patients with Richter’s transformation – a condition in which CLL transforms to a more aggressive lymphoma with currently very poor outcomes. Those trials, she says, range from testing new front-line options for patients who have new CLL diagnoses to comparing treatments for people whose recurrent cancers are not responding to newer targeted agents in the field.

“One of my priorities at Stanford is making sure that we always have trials in both of these settings,” says Fakhri. “Despite all the advances in CLL, there are still a subset of patients with high-risk features that need new treatment options, and we want to meet their needs.”

About 88% of patients newly diagnosed with CLL will survive for at least five years, according to the latest data from the National Cancer Institute. That represents a large increase from the 70% to 75% five-year survival rate in the 1990s and early 2000s. But patients who have recurrence of their cancer, even years later, often fare less well – that is one of the populations Fakhri hopes to help with new clinical trials.

Fakhri adds that the most effective CLL drugs have come out of a detailed molecular understanding of how CLL impacts cells, and this kind of basic research must continue. To that end, she is collaborating with Stanford scientists including Sydney Lu, MD, PhD, who studies the underlying biology of CLL and other cancers. Lu and Fakhri are studying the implications of a gene mutation, known as SF3B1, that is found in about one in 10 CLL cancers and is associated with worse outcomes for patients. If they can understand the molecular consequences of SF3B1, Fakhri says, they may be able to develop new drugs to counteract the mutation or develop a better understanding of the clinical behavior and response to different therapies in patients harboring the SF3B1 mutation.

There, she first encountered immunotherapy, then an emerging treatment that uses the body’s immune system to fight cancer. This experience solidified her fascination with oncology – a field where innovations could rapidly transition from the lab to clinical use, offering new hope to patients.

Immunotherapy, particularly treatments known as checkpoint inhibitors, was a revelation to Betof Warner. Unlike traditional chemotherapy, which can be relentless and without a guarantee of lasting effectiveness, immunotherapy offers the possibility of long-lasting responses from limited durations of treatment. 

How Do Checkpoint Inhibitors Work?

T cells’ inherent job in the body is to kill things that don’t belong. That can include viruses, bacteria, or even cancer. “Cancer is good at developing ways to hide,” explains Betof Warner. “I often compare this to Harry Potter’s invisibility cloak – cancer puts on an invisibility cloak to evade detection. The purpose of checkpoint inhibitor drugs is to remove that cloak, allowing the immune cells, specifically T cells, to see and attack the cancer. These T cells have the ability to kill cancer; what they lacked was the ability to see it.

“I fell in love with the idea that we could harness the immune system to create durable responses for patients,” she says. “It meant that patients wouldn’t necessarily need to be on treatment forever. We were controlling advanced cancer and getting patients back to their lives.”

Leading a New Frontier at Stanford: Solid Tumor Cell Therapy With TILs

Though checkpoint inhibitors have improved cancer care, the majority of patients still do not achieve long-term disease control with this approach. Cellular therapy is a different strategy that utilizes expanded and/or engineered T cells to incite a durable immune response to cancer. 

At Stanford, Betof Warner leads the advanced melanoma group and oversees the development of solid tumor cell therapies. She has been at the forefront of developing a new method for treating solid tumors using tumor-infiltrating lymphocytes (TILs). This cutting-edge therapy involves surgically extracting T cells from a patient’s tumor, multiplying them in a laboratory, and then reintroducing them to the patient’s body to more effectively target and kill cancer cells. Even more exciting, this is a one-time treatment that can work for patients even when standard immunotherapy with checkpoint inhibitors has failed.

Stanford recently marked a significant milestone under Betof Warner’s leadership: becoming the first center to treat a patient with this innovative cell therapy following FDA approval. This achievement highlights the rapid progress of Betof Warner’s team and the potential of TIL therapy to provide a powerful new treatment option for cancer patients.

Stanford has been a leader in cell therapy for hematological malignancies for many years. “The opportunity to bring that expertise to a whole new population of patients is what brought me here,” Betof Warner states. “It was crucial to me that if I came here to build this program, we could start treating patients with urgency as soon as FDA approval was granted.” 

Betof Warner and her team scheduled the first surgery within hours of the FDA approval. “We had a wait list of patients,” she recalls. “Being able to immediately make those phone calls after FDA approval and say, ‘I know you’ve been waiting, and here’s the day of your surgery,’ was a huge milestone.” 

Trying a new therapy is both exciting and daunting. “We want to ensure that we’re doing the right thing for the patients, but we knew we had the pieces in place here at Stanford to do it,” Betof Warner says. Now, she and her team have a full pipeline of patients.