CHRI Faculty Scholars lead the way in advancing pediatric cancer cellular therapy program

Pediatric hematologist/oncologists, Kara Davis, DO, and Norman Lacayo, MD, are leading the way in developing cancer cellular therapy programs at Lucile Packard Children’s Hospital Stanford to help patients, like Jesus Sanchez-Romero, receive treatments. (Photo credit: Stanford Child Health Research Institute)

Tuesday, September 25, 2018

By Laura Hedli

Pediatric cancer specialist, Kara Davis, DO, knows how taxing it is to play cat and mouse with leukemia. She is leading an effort at Lucile Packard Children’s Hospital Stanford in CAR-T cellular therapy, a very promising form of cancer immunotherapy requiring the collection of a patient’s own T cells that has to happen at the just-right time. If a child is too sick, they have too many leukemia cells. If a child has a lot of chemotherapy in their system, then it damages their T cells. There needs to be enough T cells for collection, and the T cells need to be healthy enough to withstand genetic modification in the lab. The ultimate goal is to put back into the child’s body their own modified T cells that are designed to find and attack the leukemia. 

Collecting T cells when a child relapses can be challenging and stressful for Dr. Davis and the families she cares for. Stanford’s Child Health Research Institute (CHRI) is allowing her to prepare sooner so that she can act quicker if and when the time comes. 

Dr. Davis was recently funded as an Anne T. and Robert M. Bass Endowed Faculty Scholar in Pediatric Cancer and Blood Diseases and will receive $100,000 each year for the next five years (2018-2023). In August 2017, she received $100,000 for a specific project with Crystal Mackall, MD, to bank T cells of children with B-cell acute lymphoblastic leukemia (ALL).

Saving cells for a rainy day

Stanford Children’s Health is a pioneer in a new frontier of pediatric leukemia research that harnesses the power of a patient’s own immune system. 

After Dr. Davis took a fortuitous meeting with a representative from Novartis, Stanford became one of the first institutions to join what grew into a 25-center clinical trial for a CAR-T cell therapy known as Kymriah. Results from the Novartis clinical trial show Kymriah is uncommonly successful children and young adults with an aggressive B-cell ALL who are unresponsive to conventional treatment or have relapsed. Many who received this customized immunotherapy have been in remission for years.

In August 2017, Kymriah became the first cell-based gene therapy to receive approval by the Federal Drug Administration for use in humans. It also became the first cancer drug approved for a pediatric indication before an adult indication. Treatment is indicated for children and young adults up to 25 years old with B-cell ALL that is refractory or in a second or subsequent relapse.   

If we have this therapy available, what if we kind of hedge our bets and think: Who could be benefiting from this in the future? Could we at least collect their cells, put them in the bank, and save them for a rainy day if we need them?

Dr. Davis says, “If we have this therapy available, what if we kind of hedge our bets and think: Who could be benefitting from this in the future? Could we at least collect their cells, put them in the bank, and save them for a rainy day if we need them?”

The process is known as apheresis. With the support of CHRI since August 2017, Dr. Davis has banked T cells from five individuals. Two have received CAR-T cell therapy as a result. 

Apheresis accounts for about one-tenth of the hefty price tag for CAR-T cell therapy, which, overall, is $475,000. The overwhelming majority of CHRI funding—nearly $90,000 of the $100,000—covers patient costs. 

“Funding from CHRI really does allow us to be much more nimble and flexible because one huge part of getting someone to these kind of cellular therapies is having the cells,” Dr. Davis says. In tandem with her clinical trials work, she also conducts research to find biomarkers predictive of relapse in children with B-cell ALL, which may help identify eligible patients.

Jesus’ journey

Jesus Sanchez-Romero began CAR-T cell therapy in September 2018 during the week of his 26th birthday. Even though there is currently a very low level of leukemia in his body, Sanchez-Romero and his doctors decided to begin treatment now because his CAR-T cells will only be available for use through October 2018; they were banked in December 2017.

Sitting with his fiancé Marisol in a hospital room in the Bass Center for Childhood Cancer and Blood Diseases, Sanchez-Romero was talkative and warm, optimistic that his body would respond well to immunotherapy. He spoke about a restaurant that he and Marisol had visited (and loved) the night before in Mountain View, an English teacher who recently made him see writing in a new light, and how different the summer weather was in the Bay Area compared to their home outside of Fresno.

Sanchez-Romero was diagnosed with acute lymphoblastic leukemia (ALL) when he was 18 years old. While he was technically an adult, at 19, he was transferred from Madera Children’s Hospital to Lucile Packard Children’s Hospital. He says he feels fortunate to be treated within pediatrics.

Indeed, Stanford’s Adolescent and Young Adult Cancer Program was designed with individuals like Sanchez-Romero in mind. It provides holistic care for teens and young adults ages 15-29.

Acute lymphoblastic leukemia is the most common form of childhood cancer, with about 3000 cases diagnosed annually. The disease progresses rapidly, as bone marrow produces too many immature lymphocytes, or white blood cells, and is unable to fight off infections. Typically, childhood ALL is highly responsive to treatment and about ninety percent of children who are diagnosed achieve remission after receiving chemotherapy.

Unfortunately, Sanchez-Romero has an aggressive form of ALL. By 25, Sanchez-Romero had already experienced three relapses, and been through two bone marrow transplants and several rounds of chemotherapy.

Dr. Davis was recently funded as the Anne T. and Robert M. Bass Endowed Faculty Scholar in Pediatric Cancer and Blood Disease, which comes with $500,000 in funding over five years (2018-2023) from the CHRI. Dr. Lacayo was named the Laurie Kraus Lacob Faculty Scholar in Pediatric Translational Medicine (2016-2019); this award comes with $300,000 of funding.

Prior to receiving Kymriah, Sanchez-Romero was under the care of Norman Lacayo, MD, who enrolled him in the AbbVie clinical trial where he received an experimental oral medication, a combination of Venetoclax and Navitoclax, with chemotherapy. Dr. Lacayo was the principal investigator at Stanford for the 16-center AbbVie clinical trial. Sanchez-Romero participated in the trail knowing that CAR-T cell therapy was the ultimate goal.

“This study worked out really well for me, and Dr. Lacayo was just super excited,” says Sanchez-Romero, who was just finishing up a semester at community college (earning all As) when he relapsed in December 2017. “Dr. Lacayo was always so happy. I remember him showing me on the computer how my body was reacting.” Sanchez-Romero had braced for the typical chemotherapy side effects like nausea, vomiting and headaches, but he reports his energy remained up throughout the trial. He remembers being in the hospital joking with Dr. Lacayo, saying “I don’t feel anything. I feel fine. I shouldn’t even be here!

“So that's when Dr. Davis comes in and she explained to me the second part of the treatment of CAR-T, and she's really upfront with me. I remember her saying, ‘You look like a million bucks. You look like you're going to be strong for the treatment,’” says Sanchez-Romero. “She was really honest, really came across as a genuine person. I understood everything along the way.”

Dr. Davis and her team waited much longer to start CAR-T cell therapy for Sanchez-Romero because the leukemia did not return as quickly as they expected following the AbbVie trial. Originally, they had planned for him to receive Kymriah in March, but Sanchez-Romero was in good health come springtime. Because his cells were set to expire in October and to comply with Kymriah’s drug indication, Sanchez-Romero received treatment in September even though the leukemia was still barely detectable in his body.

After he received a one-time infusion of CAR-T cells, Sanchez-Romero said he felt well. He was discharged from the hospital a week after receiving treatment and will be monitored as an outpatient at the Bass Center for the better part of a month.

Because Sanchez-Romero has relapsed three times, he would have been a prime candidate for Dr. Davis’ apheresis study had it existed when he was first diagnosed.

Thanks to CHRI, Stanford is one of few institutions in the nation that is offering collection of T cells immediately once somebody is diagnosed with a form of leukemia characterized by a high risk of relapse. This process is not standard clinical practice and wouldn’t necessarily be covered by insurance. The apheresis study funded by the CHRI is a feasibility study in the sense that it’s allowing researchers to explore how often they use collected cells and optimal times of collection. “Can we improve our processes and also ease access to these therapies for patients?” asks Dr. Davis.

Thanks to CHRI, Stanford is one of few institutions in the nation that is offering collection of T cells immediately once somebody is diagnosed with a form of leukemia characterized by a high risk of relapse.

CHRI helps grow cancer cellular therapy program in pediatrics

For more innovative therapies like CAR-T to be available to children with pediatric leukemia and perhaps eventually other diseases, it is important to ensure faculty members have enough time to pursue research as they manage their sizeable clinical obligations.

The CHRI now supports Dr. Lacayo’s work on acute myeloid leukemia (AML) trials with St. Jude Children’s Research Hospital AML Consortium and the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium. As a CHRI faculty scholar, Dr. Lacayo is receiving $300,000 over the course of three years (2016-2019). By protecting about a third of his full-time equivalent for his clinical trial work, CHRI is supporting his efforts to grow the leukemia and developmental therapeutics programs with the Division of Pediatric Hematology/Oncology.

Currently, Dr. Lacayo serves at the co-principal investigator for the AML16 trial with St. Jude. “The challenge of AML is it’s a more heterogenic disease than ALL. There’s more difference between patients with AML than patients with ALL,” says Dr. Lacayo. He estimates that across the 10 institutions participating in the trial there will be about 250 children enrolled, with over 40 at Stanford. “Part of this study is trying to delve into the uniqueness of each patient by looking at the epigenetic makeup of each patient.”

To this end, Dr. Lacayo is providing Dr. Davis with cell samples from the three AML studies he has conducted with St. Jude: AML02, AML08, and AML16. (Each study is numbered based on the year it launched.) Applying a process similar to what she used to find a biomarker predictive of relapse with children who have ALL, Dr. Davis will use some of her faculty scholar award to support her work in finding a biomarker predictive of relapse in children with AML.

She says, “CHRI has been instrumental in supporting the growth of the cancer cellular therapies program at Lucile Packard Children’s Hospital Stanford and in improving access for our patients to these exciting, cutting-edge therapies.” 

Laura Hedli is a writer for the Division of Neonatal and Developmental Medicine in the Department of Pediatrics and contributes stories to the Stanford Child Health Research Institute.