Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

July 25, 2019
5 min read

NCCN Releases Inaugural Pediatric ALL Clinical Practice Guidelines

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The National Comprehensive Cancer Network recently released its first clinical practice guidelines for children with acute lymphoblastic leukemia. The document provides guidance on diagnosis, treatment, and supportive care for clinicians who treat the disease, which is the most common cancer affecting patients aged younger than 21 years in the United States.

Cell Therapy Next spoke with experts who were involved with creating these new guidelines to discuss their key takeaways, their potential impact on clinical practice, and its inclusion of immune effector cell treatments, such as CAR T-cell therapy.

Local Audience, Global Reach

The NCCN pediatric ALL guidelines are significant not just because they are the first to be published by the organization for this disease, but because they are the first pediatric-focused guidelines created by the NCCN since 1995, according to Patrick Brown, MD, a pediatric oncologist with the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and chair of the NCCN Guidelines Panels for Pediatric and Adult ALL.

“Most important about these guidelines is that they will serve as a starting point to what we call resource-stratified guidelines,” Brown said.

The NCCN hopes resource-stratified guidelines will be adapted in developing regions of the world that have limited resources.

“We think this is where these guidelines may have their greatest impact in terms of saving lives,” Brown told Cell Therapy Next.

Patrick Brown, MD
Patrick Brown

“With pediatric ALL that’s particularly important because high cure rates can be achieved with widely available and inexpensive medications,” he explained.

Closer to home, Brown said the guidelines have another important audience: insurers and other payers in the health care system.

“Recommendations included in the NCCN Clinical Practice Guidelines are used by CMS and many major payers for coverage determination,” Wui-Jin Koh, MD, chief medical officer of the NCCN, told Cell Therapy Next. “This has helped care providers in the management of adult cancers. Without clearly defined clinical trial specifications, many pediatric oncologists have asked NCCN to create practice guidelines for pediatric malignancies to facilitate treatment coverage decisions.”

Brown further explained that the current cure rate for ALL is about 90%, which means the ability to continue phase 3 clinical trials to improve on outcomes has become very limited.

Wui-Jin Koh, MD
Wui-Jin Koh

“We are left with a situation where a high proportion of children with ALL don’t have clinical trials available to them because standard therapies have been so effective and toxicities have been limited,” Brown said. “The time has come to establish best practices for this disease so that we can facilitate patients getting access to standardized therapies even in the absence of clinical trials for this group of patients.”


David T. Teachey, MD, is an associate professor of pediatrics in the divisions of hematology and oncology at Children’s Hospital of Philadelphia and a member of the guidelines panel. He told Cell Therapy Next that, historically, there were pediatric-focused guidelines; however, these were eliminated in the 1990s, because the vast majority of children with cancer were treated on clinical trials developed by cooperative groups, negating the need for consensus guidelines.

Nevertheless, he explained, “As the cure rates for childhood cancer have continued to improve, more and more children are treated using ‘standard-of-care’ approaches outside of clinical trials. Thus, it became apparent that consensus guidelines were needed to inform treating clinicians.”

David T. Teachey, MD
David T. Teachey

Teachey said pediatric ALL was selected by the NCCN as the first disease to develop pediatric-specific guidelines because most patients can be cured and are treated outside of clinical trials.

Pediatric ALL is an overall cancer treatment success story, so establishing clinical practice guidelines can help not only domestic clinicians but can provide a roadmap to treatment victories in areas of the world with more limited resources.

“The guidelines represent state-of-the-art standard of care based on evidence and what we believe are best practices for this group of patients,” Lewis B. Silverman, MD, director of clinical research and clinical care in the department of pediatric oncology at Dana-Farber Cancer Institute, told Cell Therapy Next.

As a member of the guidelines panel, he said they “represent options on ways to approach these patients because there are many successful therapies that exist.”

Koh said that options are critical in providing care in low-resource settings, such as sub-Saharan Africa, where there are few if any pediatric oncology specialists. In this area of the world, general clinical oncologists routinely provide pediatric care, and pediatric-specific guidelines are especially useful in these settings.

“Our global partners have strongly requested practice guidelines for pediatric malignancies to help them provide best available care,” Koh said. “Of note, certain pediatric cancers are far more common in other regions of the world — for example, Burkitt lymphoma, which was first described in Uganda, is endemic in equatorial Africa.”

The Rise of Cell-Based Immunotherapy

The NCCN’s pediatric ALL guidelines also address the use and supportive care of patients receiving CAR T-cell therapy, specifically tisagenlecleucel (Kymriah, Novartis), an FDA-approved CD19-directed CAR T-cell immunotherapy for pediatric patients with relapsed or refractory ALL.

“Recent breakthroughs in immunotherapies and precision-medicine targeted therapies have changed the paradigm in ALL, providing novel therapies for high-risk patients and those who relapse,” Teachey said. “Many of these new therapies are highly effective, improving cure rates often with less treatment-related morbidity and mortality, and trials using tisagenlecleucel demonstrated remarkable remission rates and durable cures in many very refractory patients.”

Lewis B. Silverman, MD
Lewis B. Silverman

CAR T-cell therapy, immunotherapy’s latest breakout start, is not the only cell-based therapy addressed in NCCN pediatric ALL guidelines, Brown explained.

The guidelines also include recommendations for use of the bispecific T-cell engaging antibody called blinatumomab (Blincyto; Amgen) for relapsed or refractory ALL or MRD-positive ALL.

“The guidelines also discuss unapproved immunotherapies that are currently in clinical trials that should be considered by clinicians and their patients when indicated,” Brown said.

Silverman acknowledged that immunotherapy and CAR T-cell therapy are exciting new treatments.

“Where we are now vs. where people hope we will be regarding the effectiveness of these therapies is an important distinction that we dealt with in these guidelines,” he said.

“There is a lot of hope around CAR T therapy, but we made sure to include in these guidelines what the evidence supports and what the FDA has approved in terms of treatment.”

The NCCN announced that it would continue to publish new pediatric guidelines until it addresses 90% of pediatric cancers. It plans on establishing guidelines for Burkitt lymphoma by the end of 2019 and has already starting assembling panels for pediatric Wilms tumor and Hodgkin lymphoma guidelines.

“The goal of the NCCN guidelines in oncology is to develop evidence-based and consensus-driven management recommendations for the treatment, prevention, diagnosis, and supportive care of patients with cancer,” Teachey said.

“It is important to highlight the guidelines are continuously updated to reflect new data and therapies. The NCCN guidelines provide recommendations for standard cytotoxic regimens that have existed for decades, as well as new agents and breakthrough medications such as tisagenlecleucel. The therapeutic landscape is changing at a rapid pace and the NCCN guidelines have the flexibility to adapt quickly to new data.” – by Drew Amorosi

Pediatric ALL Guidelines

Disclosures: Brown reports scientific advisory board roles with Novartis, Jazz Pharmaceuticals and Servier and use of Amgen’s publication support services. Teachey reports advisory board roles with for La Roche, Amgen and Janssen and institutional research funding (to CHOP) from Novartis. Koh and Silverman report no relevant financial disclosures.