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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.”

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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.

T-Cell Therapy Patient Story: Nicole Gularte | Emily Whitehead Foundation

 

T-Cell Therapy Patient Story: Nicole Gularte

Written by Emily Whitehead Foundation co-founder and Emily’s dad, Tom Whitehead.

Nicole Gularte is 33 years old and has relapsed with leukemia 7 times. Over the last couple of years she has been speaking in California about Emily’s treatment in between her own cancer treatments at Stanford. Nicole had her T-cells extracted, modified, and frozen awhile back in case she needed T-cell therapy. I had been messaging Nicole to encourage her to keep fighting.

On August 12th she messaged me that she was worn out, had stopped treatment three weeks earlier, and that her doctors had given her 4 to 5 weeks to live. She told me that this time her relapse was in her spinal fluid, which would disqualify her from the T-cell therapy trial, so she had contacted her doctors to tell them she was stopping all treatment. I asked Nicole what she had done since stopping treatment because I was getting strong feelings that she was going to get her modified T-cells. She told me that since stopping treatment she had been baptized and had attended several events where people prayed for her.

I told her that it was hard for me to explain, but just like when I knew Emily would survive her treatment, I had a very strong feeling that she would get her modified T-cells if she kept fighting. I explained to her that I have learned to pay attention to the whispers in my life and that if she would keep fighting we would do anything and everything to help her.

“I told her that it was hard for me to explain but, just like when I knew Emily would get through her treatment, I had a very strong feeling that she would get her modified T-cells if she kept fighting.” – Tom Whitehead

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“I told her that it was hard for me to explain but, just like when I knew Emily would get through her treatment, I had a very strong feeling that she would get her modified T-cells if she kept fighting.” – Tom Whitehead

Nicole messaged me not long after that and said ‘Thank you for inspiring me, I have now decided to get my blood checked one more time at Stanford’. She went the next day and that evening she and her mom called me crying and told me her blood came back cancer free. She went back to the doctor the next day and had a spinal tap…her spinal fluid came back clear of cancer. This meant that Nicole now qualified for the T-cell therapy clinical trial at Penn in Philadelphia, but she had lost nonrefundable flights because she was too sick to fly.

With help from some very special people, we were able to reach out to American Airlines and they donated a flight to get Nicole and her friend Janelle to Philadelphia so Nicole could get her T-cells. One of the doctor’s called me and said ‘Tom, I heard that you inspired Nicole, and I am amazed that she got results back cancer free.’ He said ‘I don’t know how to medically explain the clear blood test but I want you to know, I BELIEVE.’

Last month, Nicole received her modified T-cells and spiked a high fever due to the cytokine storm that can occur with this type of immunotherapy treatment (just like it did with Emily). She almost needed a ventilator but doctors administered tocilizumab (the same medicine that turned Emily around when she was so sick). It also worked for Nicole and she was feeling much better by the next day.

I received a message from Nicole when I was in Boston attending the International CAR-TCR Summit (a T-cell therapy conference). She told me that before she had the T-cell therapy, she had only been able to see in black and white in her left eye for the last two years due to leukemia cells in her eye…but that now she could see in full color! This was our first sign that the T-cells might be working. Nicole stayed in Philadelphia for several more weeks to recover and flew home to California earlier this week. On Thursday she received the news that her spinal fluid test came back cancer free. Then, on Friday, her doctors said her bone marrow was also free of cancer – the T-cell therapy worked! 

During Nicole’s time in Philadelphia, Kari happened to be speaking at a conference in Philadelphia, so she was able to meet and have lunch with Nicole and her friend Lia, and EWF board member Jessi Ayoub. Nicole, Lia, and Jessi also had a chance to attend Kari’s speech! You can follow Nicole’s journey on Facebook at Fighting Fire with Fire – Nicole’s Journey.

Kari and I receive calls and emails from patients from around the world more than once a week. We are working very hard to continue expanding the Emily Whitehead Foundation while we both work full-time jobs but there just never seems to be enough hours in the day! Talking with patients who need help now to survive always comes first. I hope to get the time to continue to update on other patients we are currently helping. Many patients still find out about these innovative treatments such as T-cell therapy too late.

We will continue to raise awareness for this treatment and help patients as much as we can. When Kari and I speak at events we always tell the story of how all of your prayers and positive thoughts helped our family get through Emily’s treatment. To continue growing our foundation we could use any help you can provide such as holding fundraisers and joining The Villagedonating, sharing your story, or sharing information from our website or these blog posts, so we can continue to reach other patients. Together we can make a difference!

For all the families who fought with us – we think of all of you every day especially those courageous warriors who cancer took from us. You inspire us to never stop trying to make a difference. I will continue to listen to the whispers and act on them in the hope that some day many more families will be changed for the better because their loved one survived just like our Emily.

We plan to continue sharing other patient’s stories here on our blog, including a patient who will receive the T-cell therapy this week!

Listen to the Whispers / We Believe!

~Tom