Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis

Abstract

Background: Multiagent chemotherapy is the primary treatment for acute lymphoblastic leukemia (ALL), of which asparaginases including Escherichia coli L-asparaginase (E. coli L-Asp) and pegylated-asparaginase (PEG-Asp), are cornerstone components. The study aimed to conduct a meta-analysis to compare the efficacy and safety of PEG-Asp with E. coli L-Asp in Chinese children with ALL. Methods: A systematic literature search was conducted to collect randomized controlled trials (RCTs) on PEG-Asp versus E. coli L-Asp in Chinese children with ALL. Two reviewers independently selected articles and extracted data. Risk-of-bias assessment was conducted with Cochrane recommendation tool. Pooled estimates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all outcomes in Review Manager 5.3. Results: Out of the 470 publications screened, 15 studies were included, involving 1,194 patients. Pooled estimates showed that there were no significant differences in complete responses (CR), overall response rate (ORR), gastrointestinal symptoms, and coagulation abnormalities rate between the PEG-Asp and E. coli L-Asp groups (all P>0.05). Hypersensitivity (RR =0.63; 95% CI, 0.40-1.01; Ρ=0.05) and hepatic injury rate (RR =0.45; 95% CI, 0.27-0.75; Ρ=0.002) were lower in the PEG-Asp group. The frequency of administration and length of hospital stay of patients in the PEG-Asp group were less than those in the E. coli L-Asp group (both Ρ<0.0001).Conclusions: Current evidence pointed out a similar efficacy in the two groups. The PEG-Asp group showed a lower hypersensitivity and hepatic injury rate. In addition, using PEG-Asp decreased the frequency of administration and the length of hospital stay, which, to some extent, might reduce patients' burden caused by medical resource consumption.

A Pilot Study Conducted at a Tertiary Cancer Care Center, Evaluating the Serum Asparaginase Activity in Children Suffering from Acute Lymphoblastic Leukemia after the Administration of Biosimilar Pegaspargase

“…Additionally, the use of PEG Asparaginase in pharmacotherapy may lessen the financial burden associated with using medical resources because of decreased administration frequency and a shorter length of hospital stay. 12…”

Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

“…These two trials contributed to an expanded approval for pegaspargase in 2006 for the firstline treatment of patients with ALL (20). More recently several large systemic reviews have reinforced these early findings and demonstrated superiority of pegaspargase in comparison to native E. coli asparaginase (23)(24)(25). Cost effectiveness of pegaspargase in comparison to native E. coli asparaginase has also been demonstrated (26).…”

Laporan kasus berbasis bukti: Reaksi hipersensitivitas terhadap pegylated asparaginase dibandingkan L-asparaginase pada anak dengan leukemia limfoblastik akut

“…Terdapat beberapa kekurangan pada studi metaanalisis oleh Dai dkk. 10 Pertama, studi yang dimasukkan semua dipublikasi di China dengan skala kecil. Kedua, penilaian risiko bias menggunakan Cohrane recommendation tool menunjukkan adanya 3/15 studi dengan risiko bias yang tinggi terkait kurangnya informasi mengenai metode yang digunakan.…”

“…Dengan frekuensi penyuntikan yang lebih sedikit maka angka kunjungan ke rumah sakit berkurang dan dapat mengurangi beban biaya kesehatan. 10 Pada studi Dai dkk, 10 kelompok yang mendapat PEG-asp secara bermakna menunjukkan frekuensi kunjungan ke RS lebih sedikit dan lama masa perawatan lebih rendah (p<0,00001). Suatu studi yang menilai costeffectiveness PEG-asp dibandingkan L-asp di Inggris mendapatkan bahwa PEG-asp sebagai multi-agen kemoterapi pada anak dengan LLA lebih efisien.…”