Physicians and researchers at MSK Kids, Memorial Sloan Kettering Cancer Center’s dedicated pediatric cancer program, completed several groundbreaking research studies in 2023. These studies, which focused on pediatric disease mechanisms, paved the way to promising new therapeutic approaches for improving patient outcomes.
“MSK Kids is the largest pediatric cancer program in the United States. We have a clear goal — to deliver the best possible treatment for each child entrusted to our care, and to learn from each patient,” says Andrew Kung, MD, PhD, physician-scientist and Chair of the Department of Pediatrics at MSK. “Our pediatric specialists collaborate with faculty across MSK on research and in the clinic to provide optimal care and drive new discoveries for cancers affecting infants to young adults.”
Below are six areas that saw important research and clinical advances for MSK Kids in 2023:
Cancer Genomics Reveals Evolution of Pediatric Cancers
MSK Kids is a pioneer in using whole genome sequencing (WGS) to drive discovery and guide clinical decision-making. We published two landmark papers using WGS to provide new insights into the evolution of pediatric and young adult cancers:
- Neuroblastoma: MSK Kids investigators discovered malignant neuroblastoma clones arise early in development and can spread to metastatic sites before eventual diagnosis in childhood. Tumor heterogeneity and evolution have important implications for response to therapy and potential disease relapse. The inclusion of agents targeting all subclones in upfront therapy will be important for improving the chance of a cure in patients with high-risk neuroblastoma. The study was published in Nature Genetics. (1)
- Osteosarcoma: The research team found that chemoresistant osteosarcoma subclones are often present at diagnosis, and resistant clones emerge under selective pressure from neoadjuvant chemotherapy. Resistant clones have unique amplifications and genetic alterations. In the future, targeting these resistance-associated changes during upfront therapy may be an effective strategy for eliminating resistant tumor subclones and improving survival. MSK Kids researchers led the study published in Cancer Research. (2)
Cell Therapies for Curing Non-Malignant Diseases
Building on MSK’s 50-year history of leadership in stem cell and bone marrow transplantation, MSK Kids continues to pioneer cell therapies for definitive cures of non-malignant diseases, such as Fanconi anemia, sickle cell disease, and dysregulated immune conditions:
- Sickle cell disease: Together with colleagues from other centers, MSK Kids researchers conducted a groundbreaking phase 1/2 clinical trial (NCT04443907) testing the autologous CRISPR-Cas9 gene-edited cell therapy OTQ923. The novel cell therapy induced fetal hemoglobin in 70% to 88% of red cells, lessening disease severity over a follow-up period of 6 to 18 months in three young adult patients with severe sickle cell disease. The study was published in The New England Journal of Medicine. (3)
- Fanconi anemia: A multi-institutional retrospective study led by MSK Kids investigators revealed allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia provided excellent survival odds and low toxicity, particularly in patients under 19. The study demonstrated that matched unrelated donors and cord blood were good cell sources for patients without suitably matched sibling donors. The study was published in Bone Marrow Transplantation. (4)
- Primary Immune Regulatory Disorder (PIRD): MSK Kids successfully cured a 6-year-old girl with a PIRD caused by a STAT1 gain-of-function mutation. After dampening hyperimmune reactivity with the interferon blocker emapalumab as a bridge to HCT, the patient achieved full T cell donor chimerism at three months and 100% donor chimerism with no graft-versus-host disease at one year post-HCT. MSK researchers and colleagues at other centers published their findings in the Journal of Allergy and Clinical Immunology. (5) MSK is now leading a phase 2 clinical trial (NCT05787574) investigating emapalumab in a larger group of patients with PIRD as a bridge to HCT.
Data Science Finds New Treatments for Pediatric Cancers
MSK Kids researchers continue to leverage novel data science approaches to reveal oncogenic gene mutations and aberrantly activated pathways that may be exploited for therapeutic benefit:
- Two new tools for predicting drug response in patients: Investigators from MSK Kids and Columbia University Irvine Medical Center collaboratively validated two complementary RNA-based assays that predict actionable drug responses. OncoTarget identifies high-affinity inhibitors of cancer-driving master regulator proteins, and OncoTreat identifies drugs that invert the transcriptional activity of hyperconnected master regulator protein modules. Agents identified by these tools achieved significant disease control rates of 68% and 91%, respectively, and 15 of 18 drugs identified by OncoTreat inverted the predicted master regulator module activity in patient-specific xenograft models. The findings were reported in Cancer Discovery. (6)
- Malignant rhabdoid tumor and Wilms’ tumor: MSK Kids investigators led a systematic assessment of pediatric and adult cancers using the above approaches and found aberrant activation of the protein exportin-1 (XPO1) in two pediatric renal tumors: aggressive malignant rhabdoid tumors and Wilms’ tumors. XPO1 inhibitors had significant anti-tumor efficacy in patient-derived xenograft models of these cancers. Their paper, published in Med, (7) includes a case report of a child with multiply-relapsed Wilms’ tumor that demonstrated sustained disease control with selinexor, an XPO1 inhibitor. MSK Kids is now leading a multicenter phase 2 clinical trial (NCT05985161) based on this translational discovery.
Advancing an Age-Unrestricted Approach to Defining New Treatment Targets
Working closely with MSK medical oncologists, MSK Kids is a leader in identifying biologically-based treatment targets without age limitations, such as contributing to the approval of NTRK inhibitors and checkpoint inhibitors for mismatch-repair deficient tumors in an age-agnostic manner. Below is another example:
- Menin Inhibitor for Acute Leukemias. Following early translational work by MSK researchers on menin inhibitors, a novel class of drugs targeting NPM1 and KMT2A rearranged acute leukemias, MSK participated in a multisite phase 1/2 dose escalation clinical trial (NCT04065399) of revumenib. The selective and potent oral menin inhibitor was associated with promising antileukemic activity and a 30% rate of complete remission or complete remission with partial hematologic recovery among 68 patients, which included both children and adults with highly refractory acute leukemia with KMT2A or NPM1 mutations. The study results were published in Nature. (8)
New Immunotherapy Approaches for Pediatric Patients
Building on MSK’s long legacy of pioneering immunotherapies, MSK Kids continues to define new immunotherapeutic approaches that promise greater efficacy and reduced toxicity for solid tumors and hematologic cancers in pediatric patients.
- A novel vaccine boost for high-risk neuroblastoma. Following translational work in mice with yeast-derived β-glucan, MSK Kids investigators led a phase 2 clinical trial (NCT00911560) of adjuvant oral β-glucan during GD2/GD3 ganglioside vaccination among 107 pediatric patients with high-risk, relapsed metastatic neuroblastoma. Adding oral β-glucan during the first five weeks of vaccine priming increased the anti-GD2 IgG1 titer among responders with no additional toxicity. The study results were published in JAMA Oncology. (9)
- Brentuximab vedotin for relapsed or refractory Hodgkin lymphoma. The evidence for the anti-CD30 antibody-drug conjugate brentuximab vedotin as a consolidation therapy for autologous stem cell transplantation (ASCT) in pediatric patients with Hodgkin lymphoma are extremely limited, with only 11 cases reported in the literature. Together with colleagues from other centers in the U.S. and Canada, MSK Kids investigators conducted a retrospective study among 67 patients, the largest cohort to date. Their analysis revealed brentuximab vedotin as consolidation therapy after ASCT for relapsed or refractory Hodgkin lymphoma was associated with a three-year progression-free survival rate of 85% and was well tolerated, with a similar safety profile as in adult patients. The study was published in Blood Advances. (10)
Expertise in Pediatric Surgical Oncology
MSK Kids achieved a notable distinction this year by earning designation as the first-ever Children’s Surgery Verification (CSV) Quality Improvement Program Level I Specialty Children’s Surgery Center in Oncology by the American College of Surgeons.
MSK Kids pediatric cancer surgeons have extensive experience performing surgeries to treat patients with common and rare tumors. They perform annually about 2,500 procedures on patients under the age of 18 and about 800 procedures on young adult patients with pediatric cancers across 14 surgical subspecialties. One of the ways that set MSK’s approach apart is pairing pediatric surgeons with adult surgeons on diagnoses, treatment planning, procedures, and patient follow-ups for pediatric patients who require complex surgeries more often performed in adults. The breadth of surgical expertise across MSK makes collaboration fast and seamless. Learn more about MSK’s Approach to Complex Pediatric Surgical Oncology.
A Look Ahead
“We were pleased to welcome pediatric oncologist Damon Reed, MD, as Division Head of Pediatric Solid Tumors and Chief of the Pediatric Sarcoma Service in August. Dr. Reed is an internationally recognized sarcoma and adolescent and young adult key opinion leader who sees patients in both pediatric and medical oncology clinics,” Dr. Kung said. “I look forward to working with him as we continue to advance our efforts in research and patient care in collaboration with our team of pediatric subspecialty experts.”