POGO-FUNDED RESEARCH: An Economic Evaluation of CAR-T Therapy
Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and for most patients, the standard chemotherapy protocol works very well with an overall cure rate of 90%. But, there is a subset of this population that is treatment resistant. For these young patients, a relatively new therapy called chimeric antigen receptor T-cells (CAR-T) therapy may be the answer.
CAR-T therapy uses the patient’s own immune system to do the work of destroying the ALL cancer cells. It starts with harvesting immune cells called T-cells from a patient’s blood. Millions of copies of these cells are grown in a lab—engineered to recognize, target and destroy the cancer cells—then infused into the patient’s bloodstream. Once back in the patient’s body, the cells divide and increase in number, creating a massive army against leukemia cells. Importantly, unlike an infusion of a drug, these cells can remain in the body indefinitely, providing constant surveillance against ALL’s return. The results to date are promising, but not without significant risk.
“Like most cancer therapies, CAR-T cell treatment can have severe and potentially fatal side effects,” says Dr. Alexandra Zorzi, pediatric oncologist at Children’s Hospital, London Health Sciences Centre. “The ‘activation’ of your own immune system can lead to the release of too many cytokines, which can result in laboured breathing, high fevers, and potentially life-threatening decrease of blood flow to internal organs.”
But when it works, it works miracles. At least that is what we know in the short term. “CAR-T cell therapy has the potential to be a major game changer in childhood ALL,” says Dr. Paul Gibson, medical officer with POGO. The early results have shown remarkable response rates, even in children who have been heavily treated for ALL previously. Not only is the response rate impressive, but so are the sustained remissions many patients are experiencing. “This is the first true gene therapy in childhood cancer therapy,” says Dr. Gibson. “While very expensive upfront, it may not only save lives, but save children from needing to be treated many more times in the future.”
Currently, this therapy is only offered at the Children’s Hospital of Philadelphia. The cost to send an Ontario patient for treatment is close to $500,000, not including the cost to families who often have to leave work and home for several months.
In 2016, POGO awarded Dr. Petros Pechlivanoglou with a seed grant for his project “Economic Evaluation of CAR-T Therapy for Children with High Risk Relapsed ALL.” Dr. Pechlivanoglou and his co-investigators—Drs. Sumit Gupta, Jason Pole, Paul Nathan, Tal Schechter-Finkelstein and Wendy Ungar, together with PhD student Jill Furzer—are using statistical and mathematical modelling to determine the value of CAR-T therapy from a clinical and economic perspective. What is the trade-off between the treatment’s effectiveness and its cost to the Canadian healthcare system and society overall? Where should we focus our efforts to collect more evidence in the future? And, how will this information be used to inform policy decisions?
“This economic evaluation of CAR-T therapy is only one example of new therapies,” says Dr. Petros Pechlivanoglou. “As new cancer innovations emerge, both in the pediatric and the adult world, we are going to have this challenge of understanding the ‘value-for-money’ proposition again and again. This grant will help us tease out the methods needed to find timely answers to such questions and make prioritization decisions about future clinical, economic and policy research.” – Petros Pechlivanoglou, PhD
Dr. Petros Pechlivanoglou is a scientist at The Hospital for Sick Children Research Institute and assistant professor at the University of Toronto. His research focuses on methods around the use of health decision analysis, administrative data and prediction modelling in economic evaluation, and the health economics of pediatric oncology and pre-term birth.
The 2017 POGO Multi-Disciplinary Symposium on Childhood Cancer – Cancer in Infancy: Tiny Patients, Huge Challenges – examined clinical and scientific advances in cancer in infancy and the associated physical, psychosocial and medical issues, as well as focus on relevant resources, tools and strategies for a multidisciplinary audience.
Over 230 delegates representing a variety of disciplines attended the conference!
Click on the session titles below to view presentations that POGO has permission to share.
NOTE: The content of each presentation below captures the unedited information and opinions presented by the speakers. Please note that the information contained in the presentations was current at the time it was presented – there may be further information in subsequent literature. Listed speaker credentials were current at the time of presentation.
The Complex Nature of Neuroblastoma in Infancy
Rochelle Bagatell, MD, Children’s Hospital of Philadelphia
Developmental Outcomes for Infants with Cancer: Understudied and Underserved?
Melissa Alderfer, PhD, Nemours/A.I. duPont Hospital for Children
Retinoblastoma: An Eye to the Future
Furqan Shaikh, MD, MSc, FRCPC, The Hospital for Sick Children
BRIGHT IDEAS: An Evidence-Based Approach to Alleviate Distress in Caregivers of Children Recently Diagnosed with Cancer
Robert B. Noll, PhD, University of Pittsburgh and Children’s Hospital of Pittsburgh
In Utero Surgery: Exploring New Dimensions for Infants
Jacob Langer, MD, University of Toronto and The Hospital for Sick Children
Anti-Cancer Drug Pharmacology in Infants and Very Young Children
Clinton Stewart, PharmD, St. Jude Children’s Research Hospital
Rare Tumours of Infancy
Rajkumar Venkatramani, MD, MS, FAAP, Baylor College of Medicine and Texas Children’s Hospital
The Art and Science of Keeping Infants with Cancer Well-Nourished
Laura Collins, RD, McMaster Children’s Hospital, Hamilton Health Sciences
Debbie O’Connor, PhD, RD, University of Toronto and The Hospital for Sick Children
Measuring, Managing and Mitigating Cancer and Treatment Pain in Infants
Anna Taddio, PhD, University of Toronto and The Hospital for Sick Children
Jason Thomas Maynes, PhD, MD, The Hospital for Sick Children
Developmental and Psychosocial Aspects of Caring for Infants with Cancer
Melissa Alderfer, PhD, Nemours/A.I. duPont Hospital for Children
Vanessa Burgess, MScOT, OT Reg. (ONT), McMaster Children’s Hospital, Hamilton Health Sciences
A Fine Balance Infection Control in Infants
Michelle Science, MD, MSc, The Hospital for Sick Children
Dana Devine, PhD, Canadian Blood Services
Rochelle Bagatell, MD
Associate Professor of Pediatrics, Solid Tumor Section Chief, Division of Oncology
Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA
Dr. Bagatell is a pediatric oncologist with an interest in extracranial solid tumours. She is the solid tumor section chief at The Children’s Hospital of Philadelphia where she leads a multi-disciplinary team committed to improving outcomes for children with high-risk solid tumours. In addition, she leads clinical research efforts designed to critically evaluate current therapies for children with high-risk and relapsed neuroblastoma, and is committed to conducting studies of new therapies for this population. She is the vice chair of the Children’s Oncology Group (COG) Neuroblastoma Disease Committee, and is chair of the upcoming COG Phase 3 trial for children with newly diagnosed high-risk disease.
This session will cover unique aspects regarding the presentation and assessment of neuroblastoma in infants. Key features of the natural history of neuroblastoma in infants will be highlighted, as will molecular features of tumours occurring in our youngest patients. Issues pertaining to drug dosing and supportive care for infants with neuroblastoma will also be discussed. In addition, outcomes for infants with neuroblastoma will be compared and contrasted with outcomes in other patient groups.
Melissa A. Alderfer, PhD
Senior Research Scientist, The Center for Healthcare Delivery Sciences
Nemours Children’s Health System/Alfred I. duPont Hospital for Children, Wilmington, DE
Associate Professor of Pediatrics
Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
Dr. Alderfer completed a doctorate degree in clinical psychology at the University of Utah and a post-doctoral fellowship in pediatric psychology in the Division of Oncology at The Children’s Hospital of Philadelphia (CHOP). After fellowship, she stayed on in the Division of Oncology at CHOP and joined the standing faculty in the Department Pediatrics at Perelman School of Medicine at the University of Pennsylvania. She rose to the level of associate professor before transitioning in 2013 to her current position as a senior research scientist in the Center for Healthcare Delivery Sciences within Nemours Children’s Health System. Under the broad umbrella of healthcare delivery science, her program of research focuses on how childhood chronic illness impacts families, how families adapt and learn to manage illness and the healthcare system, and how we can intervene to improve the experience. Her research has been funded by the National Institutes of Health, American Cancer Society, and various other cancer foundations. She currently has 92 peer-reviewed manuscripts and chapters.
It is widely accepted that young age at the time of a cancer diagnosis is a risk factor for poorer neurocognitive development. Tumours and cancer treatments that impact the central nervous system are believed to disrupt the brain growth and development that uniquely characterizes the first few years of life. These concerns have led to clinical trials focused upon modifying treatment protocols to decrease CNS-related insults while maintaining survival rates. However, comparison-controlled prospective studies of the neurocognitive development of infants with cancer are scarce and empirical investigations of interventions to address the poorer developmental outcomes of those diagnosed and treated for cancer during infancy are even more rare. This presentation will provide a review of the current literature regarding neurodevelopmental outcomes and interventions for infants with cancer. It will also summarize current gaps in our knowledge and provide suggestions for moving research and clinical care forward for this special population.
Furqan Shaikh, MD, MSc, FRCPC
Staff Oncologist, Solid Tumour Section, Haematology/Oncology
Project Investigator, CHES, Research Institute
Director, Fellow’s Continuity Clinic
The Hospital for Sick Children, Toronto, ON
Assistant Professor, Paediatrics
University of Toronto, Toronto, ON
Dr. Furqan Shaikh received his medical degree from Queen’s University in 2003. He completed his pediatrics residency at the Children’s Hospital of Eastern Ontario in Ottawa and a fellowship in Paediatric Haematology/Oncology at The Hospital for Sick Children in Toronto. Dr. Shaikh is a paediatric oncologist in the Solid Tumour Program within the Division of Haematology/Oncology at The Hospital for Sick Children, and an assistant professor of paediatrics at the University of Toronto. He is a member of the Germ Cell Tumor subcommittee of the Children’s Oncology Group.