Pegaspargase: A Review in Acute Lymphoblastic Leukaemia

Abstract

Pegaspargase (Oncaspar ® ), a pegylated form of native Escherichia coli -derived l -asparaginase (hereafter referred as E. coli l -asparaginase), is indicated in the USA and EU for the treatment of acute lymphoblastic leukaemia (ALL) as a component of multi-agent chemotherapy in paediatric and adult patients. Relative to E. coli l -asparaginase, pegaspargase has a prolonged circulation time, thereby offering less frequent administration. Moreover, pegylation of E. coli l -asparaginase may diminish the immunogenicity of the enzyme. Based on extensive evidence, intramuscular (IM) or intravenous (IV) administration of pegaspargase as a component of a multi-agent chemotherapy is an effective first-line treatment for paediatric and adult patients with ALL, as well as for the treatment of paediatric and adult patients with ALL and hypersensitivity to E. coli l -asparaginase. Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring adverse events being generally consistent to that seen with E. coli l -asparaginase. Pegaspargase treatment in patients with relapsed ALL and hypersensitivity to E. coli l -asparaginase had a similar tolerability profile to that observed in patients with newly diagnosed ALL. Given the potentially reduced immunogenicity and more convenient dosage regimen over E. coli l -asparaginase, pegaspargase remains an important and effective treatment option for paediatric and adult patients with ALL, including those with hypersensitivity to E. coli l -asparaginase. Electronic supplementary material The online version of this article (10.1007/s40265-019-01120-1) contains supplementary material, which is available to authorized users.

The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma

“…Fortunately, asparaginase-based regimens significantly improve the prognosis [24]. The rationale behind using asparaginase agents as an anti-cancer treatment is that normal lymphocytes have the asparagine synthetase enzyme and can promote the biosynthesis of their own asparagine, whereas this does not occur in lymphoma cells [25]. Thus, those agents showed more cytotoxicity on malignant lymphocytes than normal cells, leading to a decrease in lymphocytes [26–28], which probably explained why the LMR level in high LMR group decreased significantly when treatment response was achieved in the present study, and the incidence of infection increased during the treatment of asparaginase agents [27, 28].…”

Tumor Metabolism as a Regulator of Tumor–Host Interactions in the B-Cell Lymphoma Microenvironment—Fueling Progression and Novel Brakes for Therapy

“…In this line, the use of pegaspargase is an established clinical practice, which hydrolyses asparagine into aspartic acid and ammonia and is implemented in a multiagent chemotherapy in first-line treatment of ALL [171,207]. Here, pegaspargase was shown to mediate inhibited protein, DNA-, and RNA-synthesis, and to induce cell death in ALL [208]…”

Preclinical developments of enzyme-loaded red blood cells

“…PEGylated formulations of the therapeutic enzyme were developed to overcome these limitations and were firstly used in clinical trials in the 1980s. However, the administration of PEGylated asparaginase was associated with hepatotoxicity, pancreatitis, and thrombosis [49], paving the way for alternative delivery strategies. Again, the possibility to administer the enzyme confined into RBCs has been explored in animal models.…”