NCCN Adds Rylaze to Clinical Practice Guidelines for Acute Lymphoblastic Leukemia

Luke Maese, DO

Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for the treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL), announced Jazz Pharmaceuticals, developer of the agent, in a press release.¹

The addition of the treatment strategy follows the FDA’s approval of asparaginase to be used as a component of a multi-agent chemotherapeutic regimen administered by intramuscular injection for the treatment of ALL and lymphoblastic lymphoma (LBL) in adult and pediatric patients aged 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.²

“ALL is the most common cancer of childhood, but we’ve done a great job over the past century of improving survival rates. This is due in large part to asparaginase and its incorporation into therapy. But with knowing that there are adverse events [AEs] from these medications, it’s important to have a second-line option available for patients,” said Luke Maese, DO, an associate professor of pediatrics at the University of Utah - Huntsman Cancer Institute, Division of Pediatric Hematology/Oncology at Primary Children's Hospital during a July 20 webcast, hosted by Jazz Pharmaceuticals.³

Asparaginase earned approval based on the results from a phase 2/3 single-arm, open-label, multicenter, dose confirmation study (NCT04943952), which included 102 patients with ALL and LBL who developed hypersensitivity or silent inactivation to E. Coli-derived asparaginase. Patients in the study were assessed for the achievement and maintenance of a certain level of asparaginase activity.^1,2

At the dose of 25 mg/m2 results recently presented during a webcast by the developer showed that 93.6% of patients (95% CI, 92.6%-94.6%) maintained nadir serum asparaginase activity (NSAA) ≥ 0.1 U/mL at 48 hours after a dose of asparaginase.³

In terms of safety, the phase 2/3 study showed that the agent led to AEs in more than 15% of patients. The most common AEs were abnormal liver tests, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia. There was 1 patient who had a fatal reaction to the therapy. Moreover, serious AEs were observed in 55% of patients. Of the serious AEs, those observed most frequently were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea, and viral infection.²

Permanent discontinuation of asparaginase occurred in 9% of patients due to AEs. Of the patients who permanently discontinued therapy, 6% discontinued due to hypersensitivity and 3% discontinued due to infection.

Updated safety information showed that there were no clinically meaningful differences in safety or NSAA across the pediatric age groups, which consisted of infants, children, and adolescents.³

The drug label for asparaginase warns not to administer to patients with allergic reactions to the drug, or serious pancreatic swelling. The recommended dose is 25mg/m².¹

"Asparaginase is a core component of chemotherapeutic regimens in ALL and lymphoblastic lymphoma; however, treatments derived from E. coli are associated with the potential for hypersensitivity reactions, which can affect a substantial number of these patients," said Rob Iannone, MD, MSCE, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, in a statement. "Before the FDA approval of Rylaze, there was a significant need for an effective and reliable supply of asparaginase medicine that would allow patients the opportunity to start and complete their prescribed treatment program with confidence. We are pleased by the NCCN's decision to quickly incorporate Rylaze into the Clinical Practice Guidelines for ALL."

_References:

_{1. National Comprehensive Cancer Network® adds newly approved Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) to clinical practice guidelines in oncology for acute lymphoblastic leukemia. News release. July 22, 2021. Accessed July 26, 2021. https://bit.ly/3y7kwDP}

_{2. Jazz Pharmaceuticals announces U.S. FDA approval of Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma. News release. June 30, 2021. Accessed July 26, 2021. https://bit.ly/2UM6IzG}

_{3. Jazz Pharmaceutical Rylaze Investor Call. July 20, 2021. Assessed July 26, 2021. https://bit.ly/3l2rG8z}