PEGylated <i>E. coli</i> asparaginase desensitization: an effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase <i>Erwinia chrysanthemi</i> availability

Verma, Anupam; Chen, Karin; Bender, Cynthia; Gorney, Nathan; Leonard, W.F.; Barnette, Phillip

doi:10.1080/08880018.2019.1634778

Cited by 28 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were no adverse events related to the pegaspargase, and all patients whose asparaginase serum levels were checked had appropriate levels above the threshold of 0.1 IU/mL at 7 to 14 days after therapy. Verma et al describe the use of a similar protocol to treat five patients without subsequent hypersensitivity . In this series, one patient did not achieve therapeutic levels of asparaginase 4 to 7 days after infusion.…”

Section: Discussionmentioning

confidence: 88%

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

August

Farooki

Fulbright

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug‐supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.

show abstract

Section: Discussionmentioning

confidence: 88%

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

August

Farooki

Fulbright

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

“…A 13-step rapid desensitization protocol was utilized and SAA levels were measured between days 4-7 and days 10-14. 72 Seven patients had sustained SAA activity, one achieved therapeutic levels but showed accelerated clearance, while two did not achieve adequate levels consistent with neutralizing antibodies. Although three of the 10 patients had mild to moderate hypersensitivity reactions, all were able to receive full protocol doses after clinical intervention.…”

Section: Hypersensitivity To Pegaspargasementioning

confidence: 92%

“…Others have since duplicated the safe administration of pegaspargase, while maintaining sustained SAA levels, utilizing a desensitization protocol in patients experiencing prior hypersensitivity reactions. [72][73][74] An additional area of investigation for patients who experience hypersensitivity is the COG protocol AALL1931 (NCT04145531) an open-label, multicenter study for patients with ALL/LLy following hypersensitivity to E. coli derived asparaginase with the objective to determine the efficacy, safety, and tolerability of IM recombinant crisantaspase Pseudomonas fluorescens.…”

Section: Hypersensitivity To Pegaspargasementioning

confidence: 99%

Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review

Bender¹,

Maese²,

Carter-Febres³

et al. 2021

BLCTT

Self Cite

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi, have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts. Pegaspargase, a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase, has become an integral component of pediatric upfront and relapsed ALL protocols due to its longer half-life and improved immunogenicity profile compared to native asparaginase preparations. Over the past two decades great strides have been made in outcomes for pediatric ALL due to risk stratification, incorporation of multiagent chemotherapy protocols, and central nervous system prophylaxis with pegaspargase having played an important role in this success. However, adolescents and young adults (AYA) with ALL when treated on contemporaneous trials using adult ALL regimens, continue to have poor outcomes. There is increasing realization of adapting pediatric trial regimens for treating AYAs, especially those incorporating higher intensity of chemotherapeutic agents with pegaspargase being one such agent. Dose or treatment-limiting toxicity is observed in 25-30% of patients, most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis, and dyslipidemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival leading to higher risk of relapse, and in cases of relapse, a higher risk for remission failure. This article provides an overview of available evidence for use of pegaspargase in pediatric acute lymphoblastic leukemia.

show abstract

“…Although there has been documented success with reexposure to PEG-asparaginase following hypersensitivity reactions with premedication use and intensive care monitoring, this approach remains unsuccessful in a subset of patients. 43 In contrast, a primary preventive approach with premedication is inexpensive, utilizes readily available medications, and is associated with limited adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Premedication prior to PEG‐asparaginase is cost‐effective in pediatric patients with acute lymphoblastic leukemia

McCormick

Lapinski

Friehling

et al. 2021

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background: PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions.Procedures: This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. Results:In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. Conclusion:Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

show abstract

PEGylated E. coli asparaginase desensitization: an effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase Erwinia chrysanthemi availability

Cited by 28 publications

References 28 publications

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Clinical Utility of Pegaspargase in Children, Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia: A Review

Premedication prior to PEG‐asparaginase is cost‐effective in pediatric patients with acute lymphoblastic leukemia

Contact Info

Product

Resources

About