Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are types of blood cancer. Acute lymphoblastic leukemia is a fast-growing type of blood cancer. It happens when the body makes too many lymphoblasts, which are immature white blood cells, in the bone marrow and blood. Lymphoblastic lymphoma is a fast-growing type of non-Hodgkin lymphoma. It happens when large numbers of lymphoblasts build up in the lymph nodes and thymus gland, and these abnormal cells can spread to other parts of the body.
One of the medicines that is often used to treat ALL and LBL is called asparaginase. Two forms of this medicine exist: one made from a bacteria called E. coli, and the other, called Rylaze, which is a different form of asparginase called asparaginase erwinia chrysanthemi. Rylaze is for ALL or LBL in adults and children as young as one month old who have developed allergic-reactions to E. coli-derived asparaginase.
How Does Rylaze Treat ALL and LBL?
Rylaze works by breaking down a substance in the body called L-asparagine into smaller parts, aspartic acid and ammonia. Asparagine is an amino acid that the body can make on its own. It is needed to build proteins and support normal cell growth. Some cancer cells cannot make enough of their own asparagine, so they rely on getting it from the blood. By lowering asparagine levels, Rylaze starves and kills these cancer cells, while most healthy cells can still survive.
How Is Rylaze Used?
Rylaze is injected into a muscle.
There are two main dosing schedules based on your body surface area (which is the total size of the outside of your body, a measurement that can be used to help decide safe and accurate medicine doses):
- Every 48 hours: 25 mg/m² by IM injection
- Monday/Wednesday/Friday schedule:
25 mg/m² Monday morning
25 mg/m² Wednesday morning
50 mg/m² Friday afternoon (given about 53 to 58 hours after the Wednesday dose)
Your health care provider will decide which schedule fits best with your overall treatment plan.
Are There Any Premedications and Monitoring I Should Be Aware of?
Because allergic reactions are possible, health care providers usually give medicines like acetaminophen, an antihistamine (such as diphenhydramine), and an acid reducer (such as famotidine) 30 to 60 minutes before each dose.
Before treatment and during treatment, your care team will regularly monitor:
- Liver function tests (bilirubin and transaminases)
- Blood sugar levels
- Signs of pancreatitis, blood clots, or bleeding
What Are the Serious Side Effects of Rylaze and How Should I Manage Them?
Side effects often happen with cancer treatments, but your health care provider can help prevent or manage them. If you think Rylaze is causing a side effect, tell your health care provider right away. They may adjust your dose, temporarily stop the medicine, or discontinue it if needed to keep you safe.
Allergic reactions: Rylaze can cause serious allergic reactions, including anaphylaxis. If you have the warning signs such as rash, swelling, trouble breathing, or dizziness, get medical help right away.
Pancreatitis: Severe stomach pain may be a sign of pancreatitis (inflammation of the pancreas). Seek medical attention right away if this happens.
Blood clots (thrombosis): Watch out for symptoms like a severe headache, swelling in the arms or legs, chest pain, or shortness of breath, and contact your health care provider right away and get emergency help if these occur.
Bleeding: Report any unusual bleeding or easy bruising to a health care provider.
Liver problems: Rylaze may cause serious liver damage. Keep a watch for yellowing of the skin or eyes (jaundice), severe nausea or vomiting, or unusual bleeding and bruising, and report these to your health care provider.
Fetal harm: Rylaze may harm a fetus. Let your health care provider know if you are pregnant or may become pregnant. Those who can become pregnant should use non-hormonal birth control during treatment and for three months after the last dose because Ryalze can make hormonal contraceptives less effective. Non-hormonal birth control is any method that helps prevent pregnancy without using hormones like estrogen or progesterone; an example of this would be a barrier method like condoms.
How Was Rylaze Studied for the Treatment of ALL and LBL?
Rylaze was studied in a major phase II/III clinical trial called AALL1931. The study had two parts: one looked at injections into the muscle (IM), and the other looked at intravenous infusions into a vein (IV). Rylaze is only approved for IM use, and the results of the IM study participants are summarized below.
Each person in the study replaced the remaining doses of their long-acting E. coli-based asparaginase with a two-week course of Rylaze (six doses given Monday, Wednesday, and Friday). Chemotherapy medicines were continued as planned.
Between December 2019 and August 2021, people were enrolled at 67 sites in North America. Children and adults with ALL or LBL could join if they had a severe allergic reaction or silent inactivation (when the body makes antibodies against a medicine without causing obvious symptoms) to a long-acting E. coli-based asparaginase, and still had at least one dose left in their treatment plan. People were not eligible if they had already been treated with Erwinia-derived asparaginase or Rylaze previously, had relapsed ALL/LBL, or had a history of severe pancreatitis, blood clots, or bleeding linked to asparaginase. Relapse was defined as the leukemia coming back after it had already been treated and was in remission.
The main goal of the study was to see how many people kept their asparaginase activity level at or above 0.1 IU/mL in the first treatment course with IM Rylaze. This outcome matters because keeping the level high enough means the medicine is working to block leukemia cells from growing. Safety was checked by recording any side effects that happened during treatment, as well as those thought by health care providers to be directly caused by Rylaze.
Altogether, 228 people received at least one dose and were included in the safety review, and 224 were included in the effectiveness review. Of these, 167 were in the IM groups, which tested three dosing schedules. One group of 51 patients got Rylaze 25 mg/m² each Monday, 25 mg/m² each Wednesday, and 50 mg/m² each Friday. The other two groups either got 25 mg/m² or 37.5 mg/m² every Monday, Wednesday, and Friday.
In the IM groups, the most common age at enrollment was 10 (ranging from 1 to 25 years). Most patients were younger than 18 (87%). Most were male (62%) and White (69%), and about one-third (32%) said they were Hispanic or Latino. Overall, in this group, about 77% of patients finished all their planned doses, while 23% stopped treatment early; the most common reason for stopping treatment was having side effects.
When Rylaze was given by IM injection at different doses, 64% of people in the 25 mg/m² group, 91% in the 37.5 mg/m² group, and 90% in the 25/25/50 mg/m² group kept their asparaginase activity level at or above 0.1 IU/mL at the final 72-hour test in the first treatment course.
Simulation models also predicted that most patients would keep therapeutic levels (≥0.1 IU/mL) when Rylaze is given in certain dosing schedules, such as IM 25 mg/m² every 48 hours. At the end of treatment, 97% of patients receiving the 25 mg/m² every 48 hours were expected to still have an asparaginase activity level of at least 0.1 IU/mL at the final 48 hour timepoint.
Your results may differ from what was seen in clinical studies.
Are There Any Special Steps Required to Get Rylaze?
Rylaze is a specialty medicine. This means that you can only get it from a specialty pharmacy and that it may require prior authorization from your insurance company.
Is There Any Cost Assistance Available?
There are financial assistance options available from the drugmaker. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at www.rylazepro.com/patient-access.
