The National Comprehensive Cancer Network (NCCN) has issued guidelines for the management of children with a rare type of kidney cancer referred to as Wilms Tumor, or nephroblastoma.

The document highlights evidence-based recommendations for how to maximize benefits while minimizing toxicities in this patient population. Notably, the guidance comprises critical information for providers who treat pediatric tumors, hematologic malignancies, and other blood disorders that may be encountered relatively infrequently. The guidelines also contain diagnostic information for primary care pediatricians to ensure that the cancer is identified early and managed in a way that results in fewer toxicities for the patients.

“Keeping up with all of the current literature for the broad array of children’s oncologic and hematologic malignancies can be daunting. The NCCN Guidelines for Wilms Tumor provide compiled, annotated, and vetted recommendations for diagnosis, treatment, and follow up—in keeping with NCCN’s goals for streamlining and improving care so that patients can live better lives,” Elizabeth Mullen, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, who is also a member of the NCCN Guidelines Panel for Wilms Tumor, stated in a press release.

Wilms tumor is the most common cancer of the kidneys in children and it is known to affect those between the ages of 3 years and 4 years.3 In the majority of patients, the tumor will present in just 1 kidney, although it has been identified in both kidneys at the same time.

One factor that may increase the risk of Wilms tumor is African-American race; these children tend to be at a slightly higher risk for this cancer compared with other races. Additionally, Asian-American children may be at lower risk than children of other races. Another risk factor is having a familial history of the cancer.

Wilms tumor is also known to occur more commonly in children with aniridia or hemihypertrophy at birth; it has also been shown to occur as part of other rare syndromes like WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome.

“The treatment of Wilms tumor is guided by the results of a series of sequential clinical trials that started back in the 1960s,” Frank M. Balis, MD, professor of pediatrics, Louis and Amelia Canuso Family Endowed Chair for Clinical Research in Oncology, of the Children’s Hospital of Philadelphia/Abramson Cancer Center at the University of Pennsylvania, and chair of the NCCN Guidelines Panel for Wilms Tumor, added in the release. “Treatment approaches have been refined through these clinical trials, making treatment selection more and more complex and nuanced.”

Balis added that treatment decisions should be based on clinical and biological risk factors, the presence of unilateral versus bilateral disease, and patient response to treatment.

NCCN clinical practice guidelines in oncology (NCCN guidelines): Wilms tumor. National Comprehensive Cancer Network. Accessed February 17, 2021.

New NCCN guidelines analyze evidence for cancer type found almost exclusively in children. News release. National Comprehensive Cancer Network. February 17, 2021. Accessed February 17, 2021. 

Wilms’ tumor. Mayo Clinic website. Updated April 24, 2020. Accessed February 17, 2021. 

This article was originally published on OncLive as, "

NCCN Issues First-Ever Guidance for Pediatric Solid Tumor

Articles

The National Comprehensive Cancer Network has issued guidelines for the management of children with a rare type of kidney cancer referred to as Wilms Tumor, or nephroblastoma.

NCCN Publishes Guidelines for Pediatric Solid Tumor

Parents of pediatric patients with cancer were found to be more likely to believe misinformation about the coronavirus disease 2019 (COVID-19) than parents of children without a cancer history, according to recent research published in 

This puts oncology nurses in the prime position to talk with caregivers of pediatric patients, and show them where to find reliable information on COVID-19.

The researchers surveyed 735 parents of children between the ages of 2 and 17 – 315 parents had children who were currently in cancer treatment, while 420 had children without a cancer history. In the survey, participants were asked to rate COVID-19 information based on whether they thought it was “definitely untrue,” “likely untrue,” “not sure if untrue/true,” “likely true,” and “definitely true.” The survey included 17 common and untrue COVID-19 myths from the World Health Organization’s website.

“For the correct pieces of information, there was no difference between the parents of kids with cancer and the parent control group,” said Jeanine P.D. Guidry, PhD, assistant professor at the Virginia Commonwealth University Robertson School of Media and Culture and director of the Media+Health Lab said in an interview with 

“For the pieces of misinformation, parents of pediatric cancer patients were more likely to say, ‘this is correct information,” Guidry explained.

Eating garlic can help prevent infection with the COVID-19 virus

Gargling with or swallowing bleach will help get rid of COVID-19

Drinking a sip of water every 15 minutes can prevent COVID-19

While eating garlic or drinking water every 15 minutes are not unhealthy actions, they can become harmful if a person believes that they are protected from COVID-19 and, as a result, does not follow CDC guidelines. Drinking bleach, however, is outright dangerous, Guidry said.

Guidry explained that parents of pediatric patients with cancer already are experiencing the stress of a diagnosis, and as a result may be more included to believe in quick fixes to mitigate the anxiety of COVID-19.

Study findings supported this: Those who reported that they were more stressed were also more likely to believe misinformation about COVID-19.

“For people who are already in a very stressful situation in their lives, [the COVID-19 pandemic] just adds to it,” she said. “And the desire to see things resolved and to not have this additional level of uncertainty may make people more vulnerable to believing misinformation, because it gives a sense of reassurance.”

The development of COVID-19 vaccines is another area that is abound with myths and misinformation around it.

“I think one of the areas with misinformation that we have to be really careful of is, of course, misinformation related to the vaccine. We have a way out of this pandemic,” Guidry said, explaining that the high efficacy rates seen with the FDA-approved vaccines are very exciting.

“This is a better outcome vaccine-wise than we thought we would get. But that doesn’t mean anything if the vaccinations don’t get in people’s arms.”

Guidry said that some vaccine misconceptions are easier to dispel. For example, if a person is worried that it was not studied enough or corners were cut in the quick development process, they can be given scientific literature to read. But other theories – like powerful people putting microchips in the vaccine to track us – might be a bit harder to approach.

“Misinformation really just plays into our fears,” Guidry said.

Oncology Nurses Can Promote Reliable Info

Since oncology nurses are typically on the frontlines of communication with patients and their caregivers, they are in an ideal spot to talk about COVID-19 misinformation and how it can be harmful – especially in more vulnerable populations like children with cancer.

“Being aware that this is an issue is probably the biggest thing,” Guidry said. “People may be more vulnerable; keep an eye on that. Talk to them about preventative measures, talk to them about the vaccine. Right now, we’re not vaccinating children, but we are vaccinating parents.”

On a broader level, Guidry concluded, “If there’s 1 thing I would wish for our society, it’s a greater trust in science. It’s not perfect, but it’s the best we have.”

Guidry J, Miller CA, Ksinan AJ, et al. COVID-19–Related Misinformation among Parents of Patients with Pediatric Cancer. 

. 2021;27(2):650-652. doi:10.3201/eid2702.203285.

Parents of pediatric patients with cancer were more likely to believe COVID-19 misinformation than parents of children without cancer. 

COVID-19 Misinformation: Parents of Patients May Fall for It 

Ruxolitinib (Jakafi), when administered using a pediatric dosing algorithm, was found to elicit responses in patients with chronic graft-versus-host disease (GVHD) with acceptable safety, according to preliminary findings from a retro review presented during the 2021 Transplantation & Cellular Therapy Meeting.1

The FDA approved ruxolitinib for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older in 2019 based on its ability to achieve a high rate of objective responses, as seen in Study INCB 18424-271 (NCT02953678). Despite this progress, there are limited data and understanding on how to administer ruxolitinib in patients with chronic disease and specifically how to dose the drug.2

A retrospective review of 20 patients with chronic GVHD, 4 of whom presented with overlap syndrome was conducted with the goal of providing more understanding on dosing ruxolitinib in pediatric patients with chronic GVHD. Investigators led by YunZu Michele Wang, MD, member, Division of Bone Marrow Transplantation and Immune Deficiency and instructor, Department of Pediatrics at the University of Cincinnati in Ohio, followed a weight-based dosing algorithm by which patients < 25 kg received 2.5 mg of ruxolitinib twice daily and those whose weight was ≥ 25 kg received at 5 mg dose of ruxolitinib twice daily. Patients in the study who were also being treated with tri-azole antifungal therapy had a 50% dose reduction of ruxolitinib upfront. The study protocol allowed for progressive dose increases of up to 10 mg twice daily. Response to ruxolitinib was assessed at the time of therapy initiation as well as a minimum of 30 days after treatment was initiated. Responses were evaluated per the National Institutes of Health 2014 Criteria.

The study population was compiled of patients aged 5 to 26 years. At baseline, information obtained for each patient showed that the underlying disease in the population was beta-thalassemia, DNA ligase intravenous deficiency, chronic neutrophilic leukemia, myelodysplastic syndrome, B-cell acute lymphoblastic leukemia (ALL), Epstein-Barr Virus, and hemophagocytic lymphohistiocytosis, acute myeloid leukemia, chronic disease, hemoglobin sickle cell disease, T-cell ALL, hyper-IgM syndrome, Fanconi anemia, and chronic myeloid leukemia.

Sixteen of the patients were steroid-refractory, but there were also 4 steroid-dependent patients included in the study. As prior systemic therapy, patients received a wide range of agents, some of which were rituximab (Rituxan), imatinib (Gleevec), infliximab (Remicade), and ibrutinib (Imbruvica). Most patients had also received a steroid.

Further assessment of disease characteristics in these patients showed that for the majority, chronic GVHD had affected major organs. The skin was the site of the most impact, which was observed in 11 patients. In addition, the eyes or sclerotic skin were impacted in 7 patients each, the gastrointestinal tract was affected in 6 patients, and the lungs, liver, and genitourinary system were impacted in 3 patients each. There were 2 patients whose joints were affected by their chronic GVHD and 1 whose muscles were compromised.

At the time of ruxolitinib initiation, 16 patients were also on treatment with prednisone at a median dose of 0.5 mg/kg daily (range, 0.08 mg-1.5 mg). The median time from diagnosis to ruxolitinib dosing was 181 days (range, 17-1792 days). Ruxolitinib was administered at a median dose level of 5 mg daily (range, 2.5 mg-10 mg). Notably, 6 patients in the study received the maximum daily ruxolitinib allotment of 20 mg.

Wang et al observed a response to ruxolitinib in the skin, joints, gastrointestinal tract, liver, and muscles. A 100% response rate was observed in the group of patients with sclerotic skin chronic GVHD. In addition, 2 out of 3 patients who had lung involvement experienced pulmonary function test stabilization following treatment with ruxolitinib.

Of the responses elicited by ruxolitinib therapy, 2 were complete responses in the skin, and 12 were partial responses that occurred a median of 48 days from the time ruxolitinib was first dosed. The overall response rate observed with ruxolitinib in this study was 70%. Durable responses were achieved by 13 of the 14 responders at a median of 411 days. There was also 1 patient who achieved stable disease. In the group of 16 patients who were on steroids at the time of ruxolitinib initiation, 13 patients were in the process of being weaned or were off steroids at data cutoff. Overall, 18 patients from the 20-patient cohort were still alive at data cutoff. Wang et al observed progressive disease in 4 of the study subjects, and 2 patients died from chronic GVHD that had severely progressed.

Ruxolitinib demonstrated some ability to activate the JAK/STAT pathway in this study, according to flow cytometry histograms taken before treatment and after initiation of treatment. The 

data showed fewer cases of progressive disease after ruxolitinib.

Ten patients in the study experienced adverse events (AEs) of any grade. In some cases of grade 3 or higher AEs, Wang et al intervened by holding off on treatment. In the case of grade 3 neutropenia, however, the dose of ruxolitinib was reduced. Another intervention involved holding the concurrent myelosuppressive agent in a patient who had 

, grade 3 thrombocytopenia, and grade 4 neutropenia. The final intervention of note involved starting a patient with an 

 colitis, grade 4 thrombocytopenia, and grade 2 neutropenia on a thrombopoietin receptor agonist.

Notably, none of the study subjects developed a fungal infection or pneumocystis pneumonia while receiving ruxolitinib. There was also no infection caused by neutropenia or bleeding caused by thrombocytopenia.

Findings from this retrospective analysis imply that ruxolitinib is safe and tolerable in children with chronic GVHD. Wang et al note that high infection rates are an ongoing problem for the chronic GVHD population and based on this analysis, it is still unclear whether or not ruxolitinib increases the rate of infection for patients with chronic GVHD.

Wang YM, Teusink-Cross A, Elborai Y, et al. Ruxolitinib for the treatment of chronic gvhd in children and young adults. Presented at: Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 298.

FDA approves ruxolitinib for acute graft-versus-host disease. New release. FDA. May 24, 2019. Accessed February 9, 2021. 


This article was originally published on OncLive as, "Ruxolitinib Showcases Early Efficacy, Safety in Pediatric Chronic GVHD."

Ruxolitinib Is Promising in Pediatric Chronic GVHD

The FDA has approved crizotinib (Xalkori) for the treatment of pediatric patients 1 year of age and older and young adults with ALK-positive relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL).

The regulatory decision was based on data from Study ADVL0912 (NCT00939770), which showed encouraging antitumor activity with crizotinib in pediatric and adult patients with relapsed/refractory ALCL.

“We are proud to deliver the first biomarker-driven therapy for children and young adults with ALCL. [Crizotinib] offers a meaningful new treatment option for young patients with relapsed or refractory ALK-positive ALCL,” Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, stated in a press release. “[Crizotinib] transformed the treatment of ALK-positive non-small cell lung cancer as the first biomarker-driven therapy for that disease, and this approval is a notable milestone in our journey to continue to follow the science to address cancers with significant unmet need.”

In the open-label, multicenter, single-arm phase 1/2 Study ADVL0912, investigators evaluated the toxicities and optimal dose of crizotinib in younger patients with solid tumors or ALCL that has relapsed after a period of improvement or has not responded to treatment.

The primary end points of this trial focused on identifying the maximum-tolerated dose of the agent, as well as determining the recommended phase 2 dose. Investigators also set out to characterize the pharmacokinetics of crizotinib in pediatric patients with refractory disease.4 Key secondary end points were to define the antitumor activity of the drug in the phase 1 portion of the research, to evaluate the relationship between ALK positivity crizotinib response, the relationship between minimal residual disease status and response, to understand the palatability of the oral formulation of the agent, and to assess potential alterations in bone growth in the patient population.

A total of 121 patients were enrolled to the trial; this included 26 pediatric patients with relapsed/refractory, systemic ALK-positive ALCL who had previously received at least 1 systemic treatment. Patients who received crizotinib experienced an ORR of 88%. Of the 23 patients who achieved a response to treatment, 39% continued to respond for at least 6 months, while 22% continued to respond for at least 12 months.

Regarding safety, the toxicity profile of the agent in children and young adults with ALK-positive ALCL proved to be comparable to its use in those with ALK-positive and ROS1-positive non—small cell lung cancer. The most frequently reported toxicities included diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough and pruritis.

Additionally, the most common adverse effect determined to be grade 3 or higher in severity comprised neutropenia, lymphopenia and thrombocytopenia. Sixty-two percent of patients experienced grade 4 neutropenia, while 35% reported grade 4 lymphopenia, and 19% experienced grade 4 thrombocytopenia. Just under half of all study participants, or 46%, experienced visual disorders with crizotinib; 65% of those with ALCL reported this toxicity.

“Crizotinib represents an exciting new development in the treatment of this disease,” Meghan Gutierrez, chief executive officer at the Lymphoma Research Foundation, added in the release. “Researchers have made significant progress in our understanding of ALCL, which we hope will continue to improve treatment strategies and the options for children with ALCL. Today’s news builds upon this progress and provides hope to pediatric patients with ALCL and their loved ones.”

1. Pfizer's Xalkori (crizotinib) approved by FDA for ALK-positive anaplastic large cell lymphoma in children and young adults. News release. Pfizer Inc. January 14, 2021. Accessed January 14, 2021. http://bit.ly/35YmdaL.

2. FDA accepts supplemental new drug application for Pfizer’s Xalkori (crizotinib) for the treatment of pediatric ALK-positive anaplastic large cell lymphoma. News release. Pfizer Inc. January 14, 2021. Accessed September 23, 2020. https://bit.ly/2RRX75J.

3. Gambacorti-Passerini C, Orlov S, Zhang L, et al. Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): a phase 1b open-label study. Am J Hematol. 2018;93:607-614. doi:10.1002/ajh.25043

4. Crizotinib in treating younger patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma. ClinicalTrials.gov. Updated June 9, 2020. Accessed September 23, 2020. https://clinicaltrials.gov/ct2/show/NCT00939770.

5. Mossé YP, Voss SD, Lim MS, et al. Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: a Children's Oncology Group study. J Clin Oncol. 2017;35(28):3215-3221. doi:10.1200/JCO.2017.73.4830

FDA Approves Crizotinib for Pediatric and Young Adult ALK+ Anaplastic Large Cell Lymphoma

FDA Approves Crizotinib for Pediatric/Young Adult ALK+ Anaplastic Large Cell Lymphoma

Germline predisposition variants associated with cancer susceptibility syndromes can underlie the genetic risk for rhabdomyosarcoma (RMS), indicating that germline testing should be performed in accordance with RMS subtypes and irrespective of age, according to findings from a study published in the 

Journal of the National Cancer Institute.

Germline cancer-predisposition variants were identified in 45 patients with RMS across 15 autosomal dominant genes (7.3%; all FOXO1 fusion—negative). The enrichment of germline cancer-predisposition variants in this population was statistically significant compared with controls (1.4%; P = 1.3 x 10-22). The majority of the predisposition variants (73.3%) were identified in predisposition genes that have been linked to pediatric RMS risk, such as TP53 (Li-Fraumeni syndrome), NF1 (neurofibromatosis type I), HRAS, and BRCA2.

“Currently, there are a limited number of genes considered to cause pediatric RMS,” said He (Hurley) Li, PhD, postdoctoral associate at the Human Genome Sequencing Center at Baylor College of Medicine and first author of the study. “But our study is pointing to new genes to consider. For example, we found that the BRCA2 gene, typically associated with adult breast and ovarian cancer, may also somehow influence the susceptibility of pediatric RMS.”

“Our study highlights the utility of sequencing large numbers of children diagnosed with cancer to identify these types of changes, termed pathogenic variants,” said Philip Lupo, PhD, associate professor of pediatrics, hematology and oncology at Baylor College of Medicine, and corresponding author of the study. “Understanding the frequency of these variants in children with RMS could influence strategies for genetic testing and future surveillance of patients with a pathogenic variant, as some of these variants may predispose children to multiple cancers later in life.”

RMS is an aggressive tumor and the most common soft tissue sarcoma in children. Despite its prevalence, the genetic susceptibility of the malignancy is not as well defined compared with other pediatric malignancies.

Germline DNA from 615 patients with newly diagnosed RMS, consented through the Children’s Oncology Group, underwent whole-exome sequencing. The prevalence of cancer-predisposition variants in 63 autosomal dominant cancer-predisposition genes in these patients was compared with population controls (n = 9963).

Additional findings showed that 5 patients had well-described oncogenic missense variants in HRAS (p.G12V and p.G12S) linked to Costello syndrome.

Differences in genetic etiology were reported based on histology. Specifically, germline variants were more common in patients with embryonal versus alveolar RMS (10.0% vs 3.0%, respectively; P = .02).

Furthermore, patients with a cancer-predisposition variant were found to be younger at diagnosis (P = 9.9 x 10-4), and approximately half of germline variants (40.0%) were identified in patients aged 3 years or older, contrasting current genetic testing guidelines in patients diagnosed at an early age.

“These results may change our current decisions about when to offer genetic testing for children with RMS, which right now is focused on very young patients,” concluded Sharon Plon, MD, PhD, medical geneticist on the study team and professor of pediatrics, oncology and molecular and human genetics at Baylor College of Medicine.

Li H, Sisoudiya SD, Martin-Giacalone BA, et al. Germline cancer-predisposition variants in pediatric rhabdomyosarcoma: a report from the Children’s Oncology Group. JNCI. 2020. doi:10.1093/jnci/djaa204

Genomic assessment of cancer-predisposition landscape of pediatric rhabdomyosarcoma. News release. Baylor College of Medicine. December 30, 2020. Accessed January 4, 2021. https://bit.ly/358HHkO

TP53, NF1 Among Genetic Variants Identified as Precursors to Pediatric Rhabdomyosarcoma

“But our study is pointing to new genes to consider. For example, we found that the BRCA2 gene, typically associated with adult breast and ovarian cancer, may also somehow influence the susceptibility of pediatric RMS.”

Genetic Precursors to Pediatric Rhabdomyosarcoma Identified

The FDA approved pralsetinib (Gavreto) for adults and children aged 12 or older with advanced or metastatic 

-mutant medullary thyroid cancer (MTC) who need systemic therapy or 

 fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory.

The approval is based on findings from the open-label, multi-cohort ARROW clinical trial, where the drug was administered to 55 patients with 

-mutant MTC who received prior cabozantinib or vandetanib. Overall response rate (ORR) was 60%, with 79% of responses lasting 6 or more months.

Additionally, pralsetinib was also evaluated in 29 patients with 

-mutant MTC who did not have previous cabozantinib or vandetanib. The ORR in this cohort was 66%, with 84% of responding patients having responses that lasted 6 months or longer. Finally, 9 patients who were radioactive iodine refractory received pralsetinib. Their ORR was 89%, and all responding patients had a response of 6 or more months.

It is recommended that pralsetinib be given orally once a day at a 400 mg dose. Patients should take the medication on an empty stomach, with no food intake at least 2 hours before and at least 1 hour after medication.

The most common adverse events, which occurred in 25% or more of patients included: constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. 

Common grade 3-4 laboratory abnormalities, which occurred in at least 2% of patients were: decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.

The FDA made this approval 3 months ahead of schedule with the use of their Real-Time Oncology Review (RTOR) pilot program, as well as Assessment Aid. 

The FDA approved pralsetinib (Gavreto) for adults and children aged 12 or older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who need systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory.
 

FDA Approves Pralsetinib for RET-Altered Thyroid Cancers

The FDA has granted an accelerated approval to naxitamab-gqgk (Danyelza) for use in combination with granulocyte-macrophage colony-stimulating factor as a treatment for pediatric patients 1 year of age and older and adult patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior treatment.

The decision is supported by clinical evidence from 2 studies in patients with high-risk neuroblastoma with refractory/relapsed disease.

“Today is an important day for children living with refractory/relapsed high-risk neuroblastoma,” said Thomas Gad, founder, chairman and president, of Y-mAbs, the developer of naxitamab. “It’s very exciting to see this treatment go from being an experimental therapy used at my daughter’s bedside to now being FDA approved. On behalf of Y-mAbs, I want to thank all the patients and physicians who took part in our clinical trials and our scientific partner, Memorial Sloan Kettering, for helping us achieve this goal.”

Naxitamab is a GD2-directed monoclonal antibody, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. Naxitamab is administered to patients 3 times per week in an outpatient setting and is repeated every 4 weeks.

Initial results from the Study 12-230 trial (NCT01757626) had been presented at the 2019 International Society of Pediatric Oncology Annual Congress.2 At the meeting, data from several subsets of patients who received the agent were released.

In 28 patients with primary refractory high-risk neuroblastoma, the ORR as 78% and the 2-year PFS rate was 50%. In a subset of 35 patients with relapsed neuroblastoma resistant to salvage therapy, the ORR was 37% and the 2-year PFS rate was 36%. In 44 patients with high-risk neuroblastoma in second or later complete remission and no evidence of disease, naxitamab was given in combination with GM-CSF as maintenance therapy; this resulted in a 2-year PFS rate of 52%.

Findings from a trial (NCT03363373) detailed in a poster presentation that had recently been presented at the 2020 ASCO Virtual Meeting showed that treatment with the agent in 24 patients with relapsed/refractory high-risk neuroblastoma led to a high complete response (CR) rate of 71% (95% CI, 49%-87%) and an overall objective response rate (ORR) of 79 (95% CI, 58%-93%).

Of 16 patients who were primary refractory, the ORR with naxitamab was 88% (95% CI, 62%-98%) and the CR rate was 81% (95% CI, 54%-96%). Of 8 patients who had an incomplete response to salvage treatment, the ORR and CR rates were 63% (95% CI, 24%-91%) and 50% (95% CI, 16%-84%), respectively. Thirteen of 14 patients who had bone marrow disease at baseline experienced bone marrow clearance.

The median progression-free survival (PFS) was 42 weeks (95% CI, 26—not estimable), and the median follow-up time in patients evaluable for efficacy was 30 weeks.

With regard to safety, 88% of patients experienced at least 1 related treatment-emergent adverse event (TEAE) that was grade 3/4 in severity; these events included general disorders and administration site conditions (72%), pain (72%), vascular disorders (60%), hypotension (60%), respiratory, thoracic, and mediastinal disorders (44%), skin and subcutaneous tissue disorders (40%), and urticaria (40%), among others.

Six serious related TEAEs were reported in 5 patients: anaphylactic reaction (n = 4), pyrexia (n = 1), and respiratory depression (n = 1).

The accelerated approval is contingent on the results of the confirmatory, ongoing Study 201 trial. The study will enroll a minimum of 80 patients.

1. FDA Approves Y-mAbs’ DANYELZA® (naxitamab-gqgk) for the Treatment of Neuroblastoma. News release. Y-mAbs. November 25, 2020. Accessed November 25, 2020. https://bit.ly/3nVyHGl.

2. Y-mAbs announces naxitamab update. News release. Y-mAbs Therapeutics, Inc. October 25, 2019. Accessed June 2, 2020. bit.ly/2XrflyG.

3. Mora J, Chan GC-F, Morgenstern DA, et al. Naxitamab, a new generation anti-GD2 monoclonal antibody (mAb) for treatment of relapsed/refractory high-risk neuroblastoma (HR-NB). J Clin Oncol. 2020;38(suppl 15):10543. doi:10.1200/JCO.2020.38.15_suppl.1054.

FDA Approves Naxitamab-gqgk for Relapsed/Refractory High-Risk Neuroblastoma

FDA Approves Naxitamab-gqgk for Pediatric and Adult High-Risk Neuroblastoma

A recent study led by Bethany J. Petronio-Coia, PhD, RN, a nurse educator at the Rhode Island College School of Nursing, discovered the characteristics of “approachable” nurses caring for school-aged children who were hospitalized for cancer. From compassionate listening to syringe water fights, they shared some creative ways that nurses have managed to make their care a bit less scary. 

https://www.oncnursingnews.com/web-exclusives/a-smiling-nurse-makes-all-the-difference-in-pediatric-oncology

Podcasts

From compassionate listening to syringe water fights, children shared some creative ways that nurses have managed to make their care a bit less scary. 

Capturing the Voice of the Child in Cancer Care

Being hospitalized for cancer can be a frightening experience for a child, but a friendly and approachable nurse can make all the difference.

“For these children with an oncology diagnosis, they're very vulnerable. And many times they're excluded in decisions for their care,” said Bethany J. Petronio-Coia, PhD, RN, a nurse educator at the Rhode Island College School of Nursing. “So it's really important for pediatric nurses, and providers of all kinds that they think about and reflect on actions and words, and hopefully make some changes to improve the lives of these children.”

Petronio-Coia conducted research on what pediatric patients saw as “approachable nurses.” She shared her findings in an interview with 

: Can you give some background on your research, and why it was important to conduct? 

I've had a very varied career, all in pediatrics, but at many different capacities from home care, pediatric intensive care units, in hospital, inpatient setting, and then my experiences as a clinical nurse specialist, where I worked with pediatric hematology and oncology patients and all children. But at every level, I've noticed that health care providers and nurses really seem to struggle to communicate with children. And so what seems common sense to some may not to others. This isn't a natural behavior that everyone has. As I moved along my career, I became a nurse educator. And now I'm a professor at Rhode Island College teaching pediatrics to nursing students.

I would find my students standing outside the doors of the rooms of these children that I had assigned them. And I would go up to them and say, ‘What’s going on? Is everything okay?’ And their comment to me was not that they were afraid of being able to care for the child. But they would say, “I don't know how to talk to these kids. I'm scared. How do I talk to them?”

And so I started my doctoral work. And I started looking into communication with children and trying to find out with my literature searches, what work has been done, what hasn't been done. I found there was little to no research about communication and approachability. I started thinking about what makes a nurse approachable. I found the United Nations, they had a convention in 1989, about the rights of children. And it drew international attention. And there's been some spin off with research, but not a lot with the importance of hearing the voice of the child. So after my literature review, and really reflecting on all of my experiences as a pediatric nurse, I found, it became very transparent to me that that was where I needed to do my work.

What kind of emotional toll can a cancer diagnosis — and subsequent hospitalizations – have on a school-aged child? 

Having that diagnosis presented to you, it's difficult to fathom as a child, but as a parent also… It's unimaginable, people immediately think, ‘Oh, my gosh, what did I do wrong? The parents? Is my child going to die?’ So that diagnosis is very challenging for these families, [as is] trying to explain it to the children what's going to happen.

[Multiple hospitalizations] cause a continual sense of disruption. It’s a disruption of the line of the child, and the family or siblings. There are many factors that impinge upon the family.

The hospital becomes like a second home to these families. Many of the children I interviewed reported that the nurses who were approachable were so kind and made the hospitalization more bearable for them. The children also reported feelings of fear … when they speak to nurses who are approachable, it helps to calm them down. It eliminated some of those fears and really made a difference.

What were some of the characteristics that approachable nurses had? 

I was able to have these interviews that were open ended with children where I had some prompts. And the children described in their own words, and I will tell you, even though they were sick, they were so excited to share with me this information because they wanted to help other kids and they wanted the nurses to know they described an approachable nurse as one who was smiling and happy. They all mentioned the smile. That was an indication that made them feel comfortable… [But] they knew when it was a fake smile.

They also noted that approachable nurses were playful. These are children, play is part of their job as kids. [Nurses would do things like] dancing, making jokes, or even squirting water from syringes [without needles].

Nurses who were approachable also took the time to talk and listen to children and ask them about their fears. They felt valued and cared for when they were listening to. And interestingly, the children really wanted to hear about the nurses’ lives, too.

Being hospitalized for cancer can be a frightening experience for a child, but a friendly and approachable nurse can make all the difference.
 

A Smiling Nurse Makes All the Difference in Pediatric Oncology

TP53 was found to be the only gene with a germline de novo pathogenic or likely pathogenic variant in pediatric patients with osteosarcoma, according to findings from the Children’s Oncology Group that were published in 

Among 95 pediatric patients with osteosarcoma who underwent whole-exome sequencing, 61 de novo variants were identified in 60 genes (n = 47). Among all 240 pediatric patients with osteosarcoma, 5.4% (n = 13) harbored a pathogenic or likely pathogenic TP53 germline variant, of which nearly half (46.2%; n = 6) were de novo.

“A high proportion of rare pathogenic TP53 variants in the pediatric patients with osteosarcoma may be de novo,” Brandon J. Diessner, PhD, of the University of Minnesota, and co-study authors wrote. “The high proportion of de novo variants identified among those that are pathogenic suggests that relying on family history patterns of cancer to identify patients with osteosarcoma at risk of harboring pathogenic TP53 variants is insufficient.”

The study population comprised 240 pediatric patients with osteosarcoma who had been under the age of 20 years at diagnosis. In phase 1 of the study, 95 patients and their parents underwent whole-exome sequencing, and, in the phase 2 portion, 145 patients underwent targeted sequencing.

After recurrent rare variants from phases 1 and 2 were confirmed to be de novo or inherited via Sanger sequencing, the variants were categorized as pathogenic or likely pathogenic, variant of uncertain significance, likely benign, or benign.

Among the 61 de novo variants that were identified in phase 1, 1 was pathogenic and localized to HFE, 2 were likely pathogenic and localized to TP53, 2 were benign and localized to LEPR and FLG, 1 was a variant of uncertain significance and localized to SMARCA4, and 55 were not reported. Six variants were classified as having high impact, and 55 were classified as having moderate impact. Two patients in phase 1 had de novo variants in the TP53 gene; the other de novo variants were found only in 1 gene.

Among 145 patients who underwent targeted sequencing, an additional 11 TP53 germline variants were identified in 11 patients; 7 were pathogenic (4.8%; 95% CI, 2.0%-9.7%) and 4 were likely pathogenic (2.8%; 95% CI, 0.8%-6.9%).

Among all 240 patients, 13 (5.4%; 95% CI, 2.9%-9.1%) harbored a pathogenic (n = 7; 2.9%; 95% CI, 1.2%-5.9%) or likely pathogenic TP53 germline variant (n = 6; 2.5%; 95% CI, 0.9%-5.4%). Among the 13 TP53 variants, 6 were de novo (46.2%; 95% CI, 19.2%-74.9%). The percentage of de novo TP53 variants among all 240 patients was 2.5% (n = 6; 95% CI, 0.9%-5.4%).

Pathogenic and likely pathogenic TP53 variants were spread between amino acids 107 and 342. Among the 13 pathogenic and likely pathogenic TP53 variants, 10 (76.9%; 95% CI, 46.2%-95.0%) were missense variants that affected the DNA binding domain, 1 was a missense variant outside of the DNA binding domain (7.7%; 95% CI, 0.1%-36.0%; tetramerization domain), and 2 were nonsense variants (15.4%; 95% CI, 1.9%-4.5%).

Significant associations were not found between the set of 60 genes with a de novo variant in phase 1 (P = .91) or between clinical features and pathogenic and likely pathogenic TP53 germline variants. 

Three of the 13 patients with a pathogenic and likely pathogenic TP53 germline variant returned a questionnaire, indicating a family history that was consistent with the 2015 Revised Chompret criteria. None of these patients harbored a de novo pathogenic variant.

“The high proportion of de novo pathogenic or likely pathogenic TP53 germline variants observed suggests efforts to identify pediatric patients with osteosarcoma at risk of harboring pathogenic TP53 variants should continue to evolve, including possible universal screening for germline TP53 pathogenic or likely pathogenic variants among pediatric patients with osteosarcoma,” concluded the study authors. 

Diessner BJ, Pankratz N, Hooten AJ, et al. Nearly half of&#8239;TP53&#8239;germline variants predicted to be pathogenic in patients with osteosarcoma are de novo: a report from the Children’s Oncology Group. JCO Precis Oncol. 2020;4:1187-1195. doi:10.1200/PO.20.00087

Pediatric Osteosarcoma Harbors a High Incidence of Pathogenic TP53 Variants.

TP53 was found to be the only gene with a germline de novo pathogenic or likely pathogenic variant in pediatric patients with osteosarcoma, according to findings from the Children’s Oncology Group that were published in JCO Precision Oncology.

Childhood/AYA Cancer