Katherine Regling, DO
Alexander Glaros, MD
“You have brains in your head. You have feet in your shoes. You can steer yourself any direction you choose.” I love this book. I love Dr. Seuss. Oh, the Places You’ll Go! by Dr. Seuss reminds me of the tumultuous journey that is the treatment of pediatric cancer. Travel back in time to the 1960s, and the standard opening dialogue with parents of a child with newly diagnosed leukemia was dominated by words like “incurable” and “fatal.” Over the next 50 years, a string of quests led by pioneers in this field to improve chemotherapy options, supportive care measures, and the possibility of a cure led us to a place we never imagined we could go. Today, we live in an era of targeted treatments for hematologic malignancies that, in the case of certain leukemias, have nearly eliminated those dreaded words from our discussions.
Specifically, the discovery and extraordinary success of CD19-targeted chimeric antigen receptor T cell (CAR-T) therapies for pediatric B-cell acute lymphoblastic leukemias (B-ALLs) has revolutionized how oncologists approach relapsed, refractory disease. We now have the possibility of utilizing CAR-Ts earlier in very high-risk disease as a replacement for allogenic hematopoietic stem cell transplantation (allo-HSCT), thus avoiding associated toxicities. This groundbreaking opportunity for shift in management has identified new questions regarding the biology of disease and the ways in which CAR-Ts may be applied to other cancers. The Education Program session “Pediatric Hematological Malignancies: CARs for Kids,” (live Q&A available on demand) provides the landscape of where we were, where we have come, and where we are heading in the treatment of pediatric cancers.
Our engines are ignited with Dr. Shannon Maude of Children’s Hospital of Philadelphia, who discusses the evidence for use of CD19 CAR-Ts as an alternative to allo-HSCT in patients with relapsed, refractory disease, as well as in a subset of patients with poor-prognostic characteristics. “It’s incredible. When we were in training, many of these patients would have been told there were no further options. Now, we have hope and the ability to give them good quality of life,” reflected Dr. Maude when asked about how the option of CAR-T therapy has transformed clinical decision-making in pediatric leukemia.
The session’s chair, Dr. Rayne Rouce, of Texas Children’s Hospital revs up the discussion focusing on the use of CAR-Ts for mature B-cell and Burkitt lymphoma. She explains the hurdles that arise in treating these diseases and based on the differences in disease biology, what we may expect to see in the clinical response to CAR-T therapy. Dr. Rouce also reviews the current clinical trials in this population, what we have learned from the adult experience, and how this data can be applied best to pediatric practice.
Also in this session, Dr. Rebecca Gardner of Seattle Children’s Hospital discusses how CAR-T therapy may be brought to the roadway for other lymphoid and myeloid malignancies in pediatric patients. “The challenges of these diseases are overlapping; this session helps in the understanding of how a target is chosen and how we balance the on-target/off-tumor toxicity,” said Dr. Gardner. These barriers have prevented rapid development of immunotherapies, yet early data from studies targeting CD5, CD7, and CD38 for T-lineage malignancies have been encouraging. Myeloid diseases’ potential targets have been focused on CD123 and CD33, with special attention to the tumor microenvironment’s role in CAR-T function.
The use of CAR-Ts was first approved by the U.S. Food and Drug Administration for pediatrics, and this success has been achieved because of the robust collaborative efforts of many. “Using the gold standard beacon of hope, building on the scientific and clinical knowledge, learning to translate the roadblocks and successes to build a comprehensive story – [CAR-T] could be a blueprint for many other diseases,” said Dr. Rouce. Together, with the perseverance of physicians and the bravery of children and their families, we’ll continue to succeed. Today is our day. We will continue to move mountains.
Dr. Regling and Dr. Glaros indicated no relevant conflicts of interest.