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Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved in decades, and alternative treatment options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells and oncolytic viruses (OVs), are currently being evaluated in both adults and children with refractory solid tumors. Because pediatric solid tumors are remarkably diverse and biologically different from their adult counterparts, more research is required to develop effective treatment regimens for these patients. Here, we first summarize recent efforts and advances in treatments for pediatric solid tumors. Next, we briefly introduce the principles for CAR T cell therapy and oncolytic virotherapy and clinical trials thereof in pediatric patients. Finally, we discuss the basis for the potential benefits of combining the two approaches in pediatric patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary treatment for pediatric, adolescent and young adult patients (AYA) with relapsed/refractory B-cell acute lymphoblastic leukemia. While the landscape of immunotherapy continues to rapidly evolve, widespread use of CAR T therapy is limited and many questions remain regarding the durability of CAR T therapy, methods to avoid CAR T therapy resistance and the role of consolidative stem cell transplant. Modified strategies to develop effective and persistent CAR T cells at lower costs and decreased toxicities are warranted. In this review we present current indications, limitations and future directions of CAR T therapy for ALL in the pediatric and AYA population. [ABSTRACT FROM AUTHOR]

The Cornell Assessment for Pediatric Delirium (CAPD) was first proposed by the Pediatric Acute Lung Injury and Sepsis Investigators Network-Stem Cell Transplantation and Cancer Immunotherapy Subgroup and MD Anderson CARTOX joint working committees, for detection of immune effector cell associated neurotoxicity (ICANS) in pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy. It was subsequently adopted by the American Society for Transplantation and Cellular Therapy. The utility of CAPD as a screening tool for early diagnosis of ICANS has not been fully characterized. We conducted a retrospective study of pediatric and young adult patients (n=15) receiving standard-of-care CAR T-cell products. Cytokine release syndrome (CRS) and ICANS occurred in 87% and 40% of patients, respectively. ICANS was associated with significantly higher peaks of serum ferritin. A change in CAPD from a prior baseline was noted in 60% of patients with ICANS, 24–72 h prior to diagnosis of ICANS. The median change from baseline to maximum CAPD score of patients who developed ICANS versus those who did not was 13 versus 3, respectively (p=0.0004). Changes in CAPD score from baseline may be the earliest indicator of ICANS among pediatric and young adult patients which may warrant closer monitoring, with more frequent CAPD assessments. [ABSTRACT FROM AUTHOR]

The T‐cell engager monoclonal antibody, blinatumomab, is a potential therapeutic strategy for refractory B acute lymphoblastic leukemia after failure of CD 19 chimeric antigen receptor T‐cell therapy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) therapies such as tisagenlecleucel, indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukemia (ALL), have been associated with striking treatment outcomes and overall survival. Yet, they are also associated with unique and potentially life-threatening complications. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are generally reversible complications of CAR therapies, but many patients may require critical care support especially if they are not promptly recognized and appropriately managed by frontline healthcare staff. As CAR therapies become more widely available, it is important that inter-professional staff members be aware of general principles regarding diagnosis and management. We hypothesized that an inter-professional education (IPE) simulation-based education intervention (CAR-TEAM) would improve knowledge base and confidence regarding complications of CAR therapies among inter-professional staff. Here, we demonstrate that following CAR-TEAM training, >90% of participants demonstrated knowledge proficiency and confidence in the IPE content area. CAR-TEAM training may serve as an important tool to establish initial and continued competency among sites introducing CAR therapies. [ABSTRACT FROM AUTHOR]

Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are unique potentially life-threatening complications associated with immune effector cell (IEC) therapies. ICANS presents with varying symptoms ranging from confusion to seizure and cerebral edema. There is no consensus on the precise pathophysiology related to ICANS. The incidence of this toxicity may vary based on the specific product, underlying diagnosis and host factors. Here, we characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. We reviewed clinical characteristics, neurological severity and outcomes in pediatric and AYA patients who received IEC standard of care products from 2018-2019 at MDACC. Severity was retrospectively assessed based on ASTCT Consensus Criteria. Nine patients, median age 15.5 (range: 3-25) years received standard of care, chimeric antigen receptor (CART) IEC therapy. The primary diagnoses were pre-B cell acute lymphoblastic leukemia (ALL) (n=8) and primary mediastinal large B-cell lymphoma (n=1). Of these patients, 4 (44%) developed ICANS within a median of 8 (range: 3-27) days of CAR T cell infusion. ICANS was associated with CRS in all affected patients, occurring within a median of 6 (range: 2-7) days after CRS. Median CRS and ICANS severity grade was 2 (range 1-4) in all 9 patients. Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was obtained in 3 affected patients but only correlated to background slowing in one with aphasia. Lumbar puncture was performed in 2 patients with ICANS and was remarkable for lymphocytosis. All patients had received prophylactic anti-epileptic medication. All patients received tocilizumab for concomitant CRS and 3 received steroids. Almost half of pediatric patients receiving standard of care CART products may experience ICANS within one week CAR T cell infusion that is associated with CRS. Pleocytosis in the CSF may be due to CAR-T trafficking into the CSF and prospective studies may clarify its significance. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients. [ABSTRACT FROM AUTHOR]