Link

CELL THERAPY

Survivor: This Woman’s Battle With Leukemia Is Pointing The Way To The Future Of Healthcare

Nov 22, 2017 by Kristin Kloberdanz & Bruce Watson

In the spring of 2016, 32-year-old Nicole Gularte grew weak and lost her ability to see colors from her left eye. She knew that her leukemia had returned.

Gularte’s form of the disease was called acute lymphoblastic leukemia, or ALL. She had been in an exhausting on-and-off battle with cancer for six years, and she was desperate to avoid yet another debilitating round of chemotherapy. She wasn’t particularly thrilled when doctors told her they had gotten lucky and found two nearly perfect bone marrow matches. Long-term studies have shown that nearly half of leukemia patients who receive a bone marrow transplant die or relapse within two years.

The story of what she did next offers a fascinating look into the future of cancer treatment. She rejected the transplant and opted to let the relapse of her ALL take full hold. That allowed her to enroll in a clinical trial of a promising new cancer treatment called CAR T-cell therapy that was run by the University of Pennsylvania and Children’s Hospital of Philadelphia. “I called UPenn,” Gularte says. She made her circumstances clear to the doctors, telling them: “I’ve given up a 10-out-of-10 bone marrow transplant so I can relapse so I can qualify for your CAR-T trial.”

In cell therapy, doctors remove some of a patient’s T-cells, the immune cells that fight against infection, reprogram them to fight and kill cancer, then put them back into the patient. Developed by doctors at Children’s Hospital of Philadelphia, the treatment gained prominence after it saved a young girl named Emily Whitehead in 2012. It’s had a 93 percent success rate in trials with patients with advanced leukemia, but it’s still a very new type of therapy. A refined version of the treatment that saved Whitehead, now called Kymriah and made by Novartis, was the first CAR T-cell therapy approved by the FDA, which in August cleared it for use in children. In October, the FDA approved a second version of CAR T-cell therapy, called Yescarta and made by Kite, to treat b-cell lymphoma for adults.

Gularte next to University of Pennsylvania’s Dr. Carl June, a leading cancer researcher. Image credit: Nicole Gularte.

Most other, similar versions of the treatments are still in the testing phase. But this new form of treatment is a welcome alternative to patients who, like Gularte, find chemo dismaying and bone-marrow transplants too uncertain. “I realized that if there was a chance of something better out there, I needed to research it and come up with my own decision,” Gularte says.

The University of Pennsylvania’s adult cell therapy trials proceeded haltingly until they gained momentum in 2016, just in time for Gularte. She gained admittance to the program, and on September 7, she received her modified T-cells. Doctors had previously removed them from her body, modified them with a virus to recognize her cancer, multiplied them and transfused them back into her body.

She spent the next few days wracked with 105.8 degrees Fahrenheit fever and suffering from several seizure-like episodes as the T-cells started fighting her disease. But her temperature soon lowered, and, on the tenth day, something surprising happened. Her eyesight, which had deteriorated during her fight with leukemia, returned.

“I was half blind in one eye, and totally color blind,” she recalls. “Then, while I was watching TV, I noticed that the girls on the screen had bright green skirts.” When she had her color vision tested, she scored 13 out of 15. Soon, her T-cell levels, which plummet when leukemia patients are battling the disease, returned to normal. She was released from the hospital.

A year later, Gularte’s T-cell activity is elevated, but she is still in remission. She’s become a passionate advocate for CAR T-cell therapy. The University of Pennsylvania’s cell therapy trial is one of more than 800 studies in gene and cell therapy currently underway globally. And based on the 80 percent complete remission rates of these trials, experts anticipate that cell therapy is poised to become a major means for fighting cancer.

Top: In 2016, Nicole Gularte entered a cell therapy trial run by the University of Pennsylvania and Children’s Hospital of Philadelphia with the hopes of fighting her acute lymphoblastic leukemia. It worked, and today her cancer is still in remission. Image credit: Nicole Gularte. Above: GE scientists and others are working to accelerate the manufacturing processes of such cell therapies at the Center for Advanced Therapeutic Cell Technologies in Toronto. Image credit: CCRM.

Tens of thousands of patients per year could be receiving the treatment by 2024, and by 2030, the cell therapy industry is expected to be worth an estimated $30 billion.

While these emerging therapies bring new hope, the process to manufacture them can be lengthy and expensive, and producing enough to meet potential demand is challenging. “Now we need to help make cell therapy affordable and scalable,” says Phil Vanek, general manager for cell therapy growth strategy at GE Healthcare Life Sciences.

GE’s cell therapy business and others are racing to provide technology and processes to make that happen. In collaboration with Center for Commercialization of Regenerative Medicine (CCRM) and the Federal Economic Development Agency for Southern Ontario, they’ve embraced a new cell therapy research and process-development facility called the Center for Advanced Therapeutic Cell Technologies, which officially opened this September in Toronto. Designed to help pharma companies, university researchers, startups and technology companies scale up manufacturing faster, the new center already employs a team of more than 30 biologists, virologists, and biomedical and other engineers, from both GE and CCRM.

“We’re transitioning into the future,” says Gularte. “It’s not just about traditional drug discovery anymore, it’s now about the innovative life sciences industry, and the ways that doctors are learning to work with the body. Cell therapy could potentially eradicate many diseases. I wanted to be part of that.”

Advertisements

A Brief Introduction to the World – My Cancer Journey

Photo: Robert Urban and Nicole Gularte

Hard to FathomBy Robert Urban

We all have expectations. We have dreams. Each day we rise to a set of promises about “the weather,” about our schedules – perhaps to go to work, school or maybe to just take a day to relax. The ratio and intensity of these expectations shift as we move through the chapters of our lives. Thankfully an increasing fraction of the world’s population has the resources and freedom to live in such a way. But for many, on some unplanned day, these daily rituals and expectations will be eclipsed by news of a life-threatening disease. In the mere moments required to utter and comprehend a “we are so sorry to have to tell you” diagnosis we are transformed from an individual, a customer, a voter, a parent, son or daughter into – “a patient.” Not just a patient, but one with a lethal disease.

The world beneath falls away; gravity seems to exist but without a source. Time, meaning, cause-and-effort all distort. The aperture of our world swiftly contracts. We turn to our doctors, to medicines, to our healthcare system and to each other to plead for help. We need answers, or at least recommendations. This is not a time that we can “be patient,” to us, nothing is more urgent.

For many lethal diagnoses, remarkable progress and even curative treatments have been discovered. Every year fewer and fewer individuals die from infectious agents. Even patients infected with HIV – what was once a certain death sentence – are now living nearly full and vibrant lives, with the right medication. For most patients infected with the hepatitis C virus (HCV) now new treatments exist and more than 90 percent are, in fact, cured.

But our deepest fears are fully manifested by cancer. A condition in which our own bodies seemingly turn against us. Just a few cells to begin, then a rogue horde on a mission to kill us. But why? What have we done? Is this somehow our own fault? Will we require a deforming surgery, will we have to undergo a toxic concoction of chemotherapy? Will they use radiation on us? If we can survive it, will it provide a cure, remission or perhaps nothing at all? Could the treatment itself cause other lasting debilitations or even spawn other cancers? We have endless questions yet find few, if any, meaningful answers.

We are now a “cancer patient.” Our early expectations seem so distant and we long for “those days.” We quickly forget the dreams and aspiration of yesterday. We want to just survive. Our journey into the healthcare system is rarely one that we find rewarding, personalized or in many ways even “caring.” We are just one of many, and now just one of the unlucky ones.

But even in cancer, impressive progress is being made. And behind each (and all new treatments) are the true heroes of modern medicine – the patients who participate in clinical trials. The bravery required, to step across this line into the true unknown and into randomized clinical trials is dizzying. Will I be eligible? will I get the experimental drug (or the placebo)? If I do get lucky enough to be randomized to the active treatment group will it be too toxic, or just maybe it will be remarkably effective and put my cancer into remission? Or better yet result in a cure? For these reasons and many more, only about 4 percent of cancer patients enter into clinical trials. But it is from that small group, who withstand these uncertainties and endure the lack of answers, that we all owe a great debt. It is this group of heroes that make new treatments possible for all others.

This week we were privileged to be visited by one such hero. In her case, acute lymphoblastic leukemia had been the life changing diagnosis in her late 20’s. Her journey included numerous highly toxic treatments and seven separate heartbreaking relapses. A loss of vision, bone necrosis in both knees and more than 200 separate spinal taps, before being sent to hospice where she “expected to just die,” were just a few of the hard-to-fathom things she experienced prior to finding a means to enroll in a clinical trial. For her, the bet was placed on immunotherapy and a cutting-edge new autologous cell-based treatment called chimeric antigen receptor – T cell or “CAR-T.”

Inspired by the remarkable story of Emily Whitehead, and to the surprise of her treatment team, she declined a perfectly matched bone marrow transplant in order to be eligible. She boarded a plane and at the clinical site she promptly donated her T cells. All this on the hope to be randomized to the group that got their modified cells reinfused (instead of placebo).

She and the blinded clinical team awaited a sign, looking for any clue if the treatment was helping. They did not have to wait too long. Within days, her modified T cells were working their “miracle.” The leukemic cancer cells in her blood were vanishing. And perhaps most surprising to all, even her vision began to return. A combination of her disease and earlier treatments had her left only able to see in black-and-white. But beyond everyone’s wildest dreams, as the modified T cells continued their specialized work, even her vision was restored and restored to full color!

Hers was a story of pure struggle. Of hopes restored only to be stripped away again and again. Of confusion, pain, and suffering but also one of passion and belief. A story that holds so many messages on what we (the healthcare system) need to focus on. A vivid reminder of each patient’s vulnerabilities and the centrality of keeping them (and their families) in the center of all that we aspire to do. But perhaps most remarkably, hers is a story of a “hero.” Of stepping into the void, of finding a way. For now, she is cured and her story will pave the way for many, many that follow and on behalf of many, we are truly grateful, humbled and inspired.

The Emily Whitehead Foundation

kari-em-and-tom

Kari, Emily and Tom at the NYC Gala, 2015


A GIFT OF INSPIRATION

The Emily Whitehead Foundation (EWF) is a nonprofit company organized by Tom and Kari Whitehead on behalf of the treatment that their daughter, Emily, received in 2012.  Emily is the first pediatric patient to receive CAR T-cell therapy.  The foundation’s purpose is to raise money and awareness for childhood cancers and cancer research.  I was first diagnosed with children’s Acute Lymphoblastic Leukemia in 2010.  Facing more relapses and less options, I began to research T-cell therapy.  Emily has been my hero for nearly three years – since I first watched her T-cell story in the YouTube video, Fire with Fire, by Ross Kauffman.  Her story has kept me inspired and has given me the courage to keep fighting for T-cell therapy and awareness.  


CHALLENGES

During my struggle to gain access to CAR T-cell therapy at The University of Pennsylvania, I faced several problems that included:

  • Disqualification from the study
  • Discouragement and loss of hope
  • Loss of travel funds

FIRST CONNECTION

I first reached out to Tom in July 2016, in an effort to obtain guidance from an expert in patient care and advocacy with T-cell therapy.  Although I qualified for the CAR T-cell trial in April 2016, I experienced a relapse in the central nervous system (CNS) which immediately disqualified me from the study.  After six years of battling ALL coupled with another relapse, I began to lose hope.  I chose to reach out to the EWF, because I knew Tom and Kari Whitehead would have a great deal of knowledge and experience in T-cell therapy and patient advocacy.


SUPPORT PROVIDED 

  • Reliable source of contact
  • Patient advocacy
  • Prayer
  • Assistance with travel arrangements

SHARING AND CARING

In early August, I explained to Tom that I no longer qualified for the trial, and that I was tired of fighting.  I stopped all treatments and a Stanford pallative care team had given me three to five weeks to live.  Tom told me not to give up and said that things would fall into place.  He assured me that he and the EWF would continue to help get me out to Philadelphia for treatment. His words eased my fears and frustration.  He helped me regain focus and get back on track in my efforts.  The EWF community added me to prayer lists, while Tom made dozens of phone calls in an attempt to get me out to Philadelphia.  Tom advocated on my behalf, stood up for my rights, and encouraged me to reach out to others who once faced similar situations.

After a trip back to Stanford per Tom’s recommendation, doctors confirmed a miracle – my blood looked normal and my spinal resutls showed no leukemia cells in the CNS.  At this point I had not received chemotherapy or blood transfusions for several weeks, so it is very unusual that my labs would look so good.  This meant that I qualified for the T-cell therapy trial.  Tom immediately put me in contact with someone who quickly arranged flights for me and a friend.


OUTCOME

  • Received T-cells
  • Cancer free
  • Future advocate

WITH GRATTITUDE

I am most grateful to the Whiteheads for coming into my life during my time of need.  The EWF community restored the hope I once lost and they showed me what it was like to believe all over again.  The Whiteheads were instrumental in getting me out to Philadelphia for the CAR T-cell treatment.  The EWF’s  community had a major impact throughout my CAR T-cell journey at The University of Pennsylvania.  If not for them, I would not have received my treatment.


ABOUT THE EWF 

The EWF has created a vast community – connecting patients, parents, fighters, survivors, and supporters who help patients and families involved with T-cell therapy.  The foundation has a team of individuals who have come together to help inspire and create a brighter future for children, patients, and families.

SUPPORT FOR OTHERS

The EWF offers an array of services that can benefit patients and families who need help with:

  • T-cell therapy information
  • Sharing experiences
  • Encouragement
  • Community support
  • Awareness
  • Patient advocacy
  • Resources
  • Cancer research

HOW TO HELP

The Emily Whitehead Foundation is dedicated to raising awareness and funds for T-cell related therapy.  You can help by participating in a fundraising event or by donating.  For more information, you can visit the EWF’s website:

The Emily Whitehead Foundation 

OTHER RESOURCES

See T-cells in action!

Fire With Fire Video with Dr. Carl June

Follow Nicole and other patients journeys:

Fighting Fire with Fire – Nicole’s Journey U Penn