PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma
Abstract
Objective: Although L-asparaginase (L-ASP) is a standard treatment for lymphoblastic lymphoma (LBL),
hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase (PEG-
ASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL).
In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90
regimen (PEG-ASP-BFM-90) for adult LBL.
Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEG-
ASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.
Results: All the 30 patients, including 19 males and 11 females with a median age of 30 (range: 18–62) years,
completed 128 times of the PEG-ASP, with the median of 4 (range: 2–6) times. Patients did not receive
radiotherapy at this time. The overall response rate was 86.7% (26/30), with 50.0% (15/30) complete response and
36.7% (11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval (95% CI),
28.2%–64.8%], and the 3-year progression-free survival was 43.0% (95% CI, 25.7%–62.0%). Major adverse events
were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and
no treatment-related mortality or severe complications were recorded.
Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple
doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapy-
related deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major
advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and
physicians.
Keywords: PEG-asparaginase; lymphoblastic lymphoma; treatment
hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase (PEG-
ASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL).
In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90
regimen (PEG-ASP-BFM-90) for adult LBL.
Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEG-
ASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.
Results: All the 30 patients, including 19 males and 11 females with a median age of 30 (range: 18–62) years,
completed 128 times of the PEG-ASP, with the median of 4 (range: 2–6) times. Patients did not receive
radiotherapy at this time. The overall response rate was 86.7% (26/30), with 50.0% (15/30) complete response and
36.7% (11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval (95% CI),
28.2%–64.8%], and the 3-year progression-free survival was 43.0% (95% CI, 25.7%–62.0%). Major adverse events
were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and
no treatment-related mortality or severe complications were recorded.
Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple
doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapy-
related deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major
advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and
physicians.
Keywords: PEG-asparaginase; lymphoblastic lymphoma; treatment