Oncology Overview: Taking a Closer Look at Rylaze for ALL, LBL

Asparaginase erwinia chrysanthemi (recombinant)-rywn) (Rylaze; Jazz Pharmaceuticals) is approved for use as a component of a chemotherapy regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). It is currently available for ordering through the authorized specialty distributors Amerisource Bergen, Cardinal Health, and McKesson.^1,2

The only alternative drug to Rylaze has been on a global shortage since 2016 so this marks an important approval.² Pharmacists can play a vital role in managing patients receiving Rylaze for ALL or LBL.

Indications

Rylaze received FDA approval and orphan drug designation on June 30, 2021, as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL and LBL in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.³

The approval of Rylaze was based on data from an ongoing clinical phase 2/3 dose confirmation study evaluating pediatric and adult patients with ALL or LBL who had an allergic reaction to E. coli-derived asparaginases and have not previously received asparaginase erwinia chrysanthemi.¹

The initial study results revealed that the Rylaze dosage provided the target level of asparaginase activity in approximately 94% of patients.¹ 

Contraindications

Rylaze is contraindicated in patients with a history of:³

• Serious hypersensitivity reactions to Rylaze, including anaphylaxis
• Serious pancreatitis during previous L-asparaginase therapy
• Serious thrombosis during previous L-asparaginase therapy
• Serious hemorrhagic events during previous L-asparaginase therapy

Mechanism of Action

Rylaze works by killing cancer cells due to depletion of plasma asparagine.³

Dosage and Administration

The recommended dose of Rylaze when replacing a long-acting asparaginase product is 25 mg/m2 administered intramuscularly every 48 hours.³

Patients should have their bilirubin, transaminases, and glucose monitored prior to initiating treatment with Rylaze and every 2-3 weeks during treatment.³ Rylaze therapy may need to be held or discontinued based on the severity of adverse reactions.³

Warnings, Precautions, and Patient Counseling Points

Hypersensitivity reactions, including anaphylaxis, have occurred in 25% of patients in clinical studies, so it is important to administer Rylaze in a clinical setting with the necessary equipment and medications to treat patients, such as epinephrine, oxygen, intravenous steroids, and antihistamines.³ Patients should be educated about the signs and symptoms of anaphylaxis, such as trouble breathing and fast heartbeat, and should be advised to seek emergency medical attention if these occur.³

Additionally, Rylaze should be discontinued in patients experiencing serious hypersensitivity reactions. Patients experiencing mild pancreatitis should have Rylaze held until the signs and symptoms subside and amylase and/or lipase levels return to 1.5 times the upper limit of normal (ULN), and then treatment can be restarted.³

Rylaze should be discontinued in patients with severe or hemorrhagic pancreatitis.³ Pharmacists should educate patients about the following possible symptoms of pancreatitis: upper abdominal pain, abdominal pain that worsens after eating, nausea, vomiting, rapid pulse, and tenderness when touching the abdomen.

Rylaze should be discontinued, and appropriate antithrombotic therapy initiated if a thrombotic event occurs.³ Patients should seek emergency medical attention if they experience the following signs of thrombosis: headache, arm or leg swelling, shortness of breath, and chest pain.

Hemorrhage has occurred in individuals receiving Rylaze and patients should report any bleeding or bruising.³ Rylaze should be discontinued in patients experiencing hepatotoxicity, with symptoms including jaundice, severe nausea or vomiting, and easy bleeding or bruising.³ 

Pregnancy and Lactation

Based on animal studies, Rylaze could cause fetal harm when administered to pregnant patients;³ however, there are no studies evaluating Rylaze in pregnant women.³ Pregnancy testing is recommended in females of reproductive potential prior to starting Rylaze therapy.³

Additionally, pharmacists should counsel women of reproductive potential to use effective non-hormonal contraceptive methods during treatment with Rylaze and for 3 months after the last dose.³ There are no available data on the presence of Rylaze in human milk and the effects on a newborn child through breastfeeding.³ Therefore, women should avoid breastfeeding during Rylaze treatment and for 1 week after the last dose.³

References:

1. 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].Jazz Pharmaceuticals.June 30, 2021.Accessed August 8, 2021.http://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-rylazetm.
2. FDA approves component of treatment regimen for most common childhood cancer [News release].FDA.June 30, 2021.Accessed August 8, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-component-treatment-regimen-most-common-childhood-cancer.
3. Rylaze.Prescribing information.Jazz Pharmaceuticals; 2021. https://pp.jazzpharma.com/pi/rylaze.en.USPI.pdf.Accessed August 8, 2021.