Physicians and researchers at MSK Kids, Memorial Sloan Kettering Cancer Center’s dedicated pediatric cancer program, achieved several notable advances in 2024, including earning authorization to provide the first gene therapy for sickle cell disease and beta thalassemia, opening a new program for patients with desmoplastic small round cell tumors, translating groundbreaking tumor evolution insights into a new clinical trial strategy for patients with osteosarcoma, and leading cutting-edge research for improving patient outcomes after CAR T cell therapy.
“As one of the largest pediatric cancer programs in the United States, we are dedicated to delivering the best possible treatment for each child and learning from their experience to help others,” says Andrew Kung, MD, PhD, Chair of the Department of Pediatrics and the Lila Acheson Wallace Chair for Pediatric Research at MSK. “Our multidisciplinary pediatric specialists collaborate with experts throughout MSK in the clinic to provide exceptional care to infants, children and young adults with cancers as well as in the lab on translational research focused on improving patient outcomes.”
Below are highlights of MSK Kids’ top achievements in 2024:
The First Hospital in New York City to Offer Sickle Cell Gene Therapy
In early November, MSK Kids became the first hospital in New York City authorized to offer a novel gene therapy for patients 12 years and older with sickle cell disease and patients with beta thalassemia.
Exagamglogene autotemcel (exa-cel) (Casgevy®) is a potentially curative autologous gene therapy that promotes the production of fetal hemoglobin. Made by Vertex Pharmaceuticals, it is tailored for each patient using CRISPR/Cas9 technology.
Vertex approved MSK Kids as an Authorized Treatment Center, recognizing it as a center of excellence in bone marrow transplantation, which for decades has been the only curative option available for these hemoglobinopathies. The authorization also recognized MSK’s role as a leader in the clinical trials of gene therapy for sickle cell disease. (1)
MSK Kids treats patients with sickle cell disease and beta thalassemia through a shared care relationship with hematologists nationwide.
MSK Kids Rare Tumors Program
Given MSK Kids’ leadership in pediatric oncology, including the largest volume of pediatric sarcoma and neuroblastoma patients in the nation, many ultra-rare cancer cases are referred to us for our specialized diagnostic and treatment capabilities. The MSK Kids Rare Tumor Program was designed to optimize care and research for rare tumors, such as kidney and liver tumors.
Within the Solid Tumor Program, MSK Kids opened the Desmoplastic Small Round Cell Tumors (DSRCT) Program, which has already cared for more than 100 patients — more than any other hospital worldwide. MSK researchers were the first to describe DSRCTs in 1989 and identify the unique genetic defect used for accurate diagnosis worldwide.
At MSK Kids, every child and young adult with cancer receives genetic tumor testing through the Pediatric Translational Medicine Service as a routine part of clinical care. The results guide the creation of individualized treatment plans and inform translational research into developing new therapeutic approaches for rare tumor types.
Translating Solid Tumor Evolution Insights into the Clinic
MSK Kids is one of the very few centers with multidisciplinary expertise and sufficient patient volume to investigate tumor evolution and clonal heterogeneity, the major causes of treatment resistance and mortality in pediatric solid tumors, and translate the insights to the clinic.
For example, in a study of the evolution of recurrent or refractory osteosarcoma, MSK Kids researchers found that while clonal driver gene single-nucleotide variants and structural variants remain primarily unchanged, subclonal populations with unique amplifications are present at diagnosis, emerge after treatment, and persist as major clones in relapses. (2)
This learning led to a recent recommendation by MSK Kids to study “later strike” treatments that attack microscopic populations of cancer cells that arise during resistance and metastasis of bone sarcomas, rather than the current approach of testing first-strike-only therapies for attacking macroscopic populations of cancer cells in initial treatment settings. (3)
Collaborating physician-scientists from the MSK Kids Pediatric Sarcoma Program are now planning the Osteosarcoma Evolves (OstEvo) clinical trial for patients with osteosarcoma. The trial will seek to enroll five patients with newly diagnosed, widely metastatic disease and five with recurrent disease. Patients will undergo standard treatment, including initial chemotherapy and surgery, followed by standard second and third surgeries, with additional “second hit” and “third hit” chemotherapies after each surgery, respectively. The chemotherapies will be chosen for their potential to address the biology of surviving clones. Experts in cancer biology, surgery, interventional radiology, pathology, and computational biology will evaluate microscopic changes in DNA, RNA, and proteins, with insights informing future OstEvo strategies.
MSK Kids plans to use this same clinical research strategy for patients with metastatic Ewing sarcoma and rhabdomyosarcoma.
Expanding Cellular Therapy Options for Pediatric Malignancies
Immunotherapy was born at MSK more than 130 years ago. Since then, MSK has been at the forefront of advancing immunocellular therapeutic approaches, including the development of CAR T cell therapy. These advances have significantly expanded MSK Kids’ armamentarium of treatment options for pediatric patients with malignant and non-malignant conditions.
CAR T cell therapy has provided the largest clinical benefit for patients with leukemia. However, while most patients demonstrate an initial response, up to 50% experience reoccurence. MSK Kids researchers are collaborating with colleagues across MSK and globally to provide pediatric and young adult patients with access to new CAR T cells and develop clinical trials assessing new approaches for improving longer-term response.
For example, the MSK-exclusive pilot study of a novel armored CAR T cell therapy for acute myeloid leukemia (AML) included patients as young as 16 (NCT06017258). Developed at MSK, the CD371-targeting CAR produces interleukin-18 to stimulate CAR T expansion and activate natural killer cells. As presented at the American Society of Hematology Annual Meeting 2024, the trial results showed that the CD371-SAVVYz-IL18 CAR T cell therapy exhibited robust expansion and activity at low doses in patients with highly refractory AML. Expansion to allow treatment of children of all ages is currently in development.
MSK Kids has also teamed up researchers at Princess Maxima Hospital in the Netherlands to co-lead a global multi-center trial at 10 participating sites to evaluate targeted lymphodepletion versus standard lymphodepletion before CAR T cell therapy. The INFLUENCE Trial builds on a retrospective study led by MSK Kids that found suboptimal fludarabine exposure was associated with a 2.5-fold higher risk of relapse and a two-fold higher risk of relapse or loss of B-cell aplasia. Funded by a $4.4 million grant from the U.S. Department of Defense, the trial will open in early 2025 and has the potential to help all pediatric patients suffering from relapsed or refractory B cell acute lymphoblastic leukemia treated with CAR T cells. (4)