[6] The most common nonhematological adverse reactions of asparaginase erwinia chrysanthemi (recombinant) include abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage (bleeding), stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.
In 1963, asparaginase (ASNase) was identified as an effective antileukemic agent, and subsequent efforts were made to isolate it from bacterial sources and scale up production for clinical trials.
[16] As researchers developed deeper into ASNase treatment protocols, it became evident that different preparations of the enzyme exhibited distinct pharmacokinetic properties, necessitating tailored dosing schedules.
Ongoing research and clinical trials continue to advance our knowledge and improve outcomes in the treatment of this challenging disease.
Numerous clinical studies have been conducted to evaluate the efficacy and safety of Erwinase in the treatment of acute lymphoblastic leukemia.
These AEs can range from mild to severe and may include hypersensitivity reactions, hepatotoxicity, pancreatitis, coagulation disorders, and thromboembolism.
The main efficacy outcome measure was demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL.
[22] A further study has examined the incidence and severity of AEs in a cohort of 199 patients with acute lymphoblastic leukemia and treated with Erwinase.
Further investigations, including larger-scale clinical trials, are warranted to confirm these findings and assess the overall efficacy and safety of JZP-458 in a broader patient population.
These findings indicate that the majority of patients across all cohorts achieved the desired NSAA levels within 48 to 72 hours of JZP-458 treatment initiation.
The most prevalent nonhematologic grade 3 or 4 treatment-related AEs included febrile neutropenia (9.0%), elevated levels of alanine aminotransferase (7.8%), and nausea (5.4%).
[28][29][30] Therefore, the FDA considered the observed and simulated data as sufficient evidence to fulfill the required efficacy target, forming the basis for their decision.
Significantly, JZP-458 offers a solution to one of the prominent challenges in patient care for individuals with acute lymphoblastic leukemia/lymphoblastic lymphoma, which is the scarcity of reliable drugs.
Its dependable manufacturing process, along with its proven efficacy and safety showcased in AALL1931, makes JZP-458 a promising candidate to address this critical issue.
[2] Asparaginase produced by Dickeya dadantii (formerly called Erwinia chrysanthemi) instead is known as crisantaspase (BAN), and is available in the United Kingdom under the brand name Erwinase.
[32] One of the E. coli asparaginases marketed under the brand name Elspar for the treatment of acute lymphoblastic leukemia[32] is also used in some mast cell tumor protocols.
[33] In July 2006, the US Food and Drug Administration (FDA) granted approval to pegaspargase for the first-line treatment of people with acute lymphoblastic leukemia as a component of a multiagent chemotherapy regimen.
Pegaspargase was previously approved in February 1994 for the treatment of patients with acute lymphoblastic leukemia who were hypersensitive to native forms of L-asparaginase.
[34][35][36] In December 2018, the FDA approved calaspargase pegol-mknl, an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years.
[46] The discovery and development of asparaginase as an anti-cancer drug began in 1953, when scientists first observed that lymphomas in rat and mice regressed after treatment with guinea pig serum.
[48] After researchers comparing different kinds of asparaginases, the one derived from Escherichia coli and Erwinia chrysanthemi turned out to have the best anti-cancer ability.
[11] The FDA approval of asparaginase erwinia chrysanthemi (recombinant) (Rylaze) was based on evidence from one ongoing clinical trial (NCT04145531) in 102 children and adult participants with a type of cancer called acute lymphoblastic leukemia/lymphoblastic lymphoma.
[49] However, because it doesn't stay as long in the body, the injections need to be more frequent, with the result that total cost of treatment may be lower for the pegylated version.
Continued investigation and refinement of treatment protocols will contribute to maximizing the benefits of Erwinase therapy for patients with acute lymphoblastic leukemia.