Contributions
Abstract: EP342
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
In the AIEOP-BFM ALL 2009 study, hypersensitivity reactions (HSR) to pegylated E.coli asparaginase (PEG-ASNase) were most commonly reported in high-risk (HR) patients.1 After induction with 2 doses of PEG-ASNase 2 weeks apart, HR patients - in contrast to standard and intermediate-risk patients - received 3 doses of PEG-ASNase, one in each of the three HR blocks (HR1-3), followed by three additional doses, one in each of the three subsequent PIII blocks (PIII 1-3).
Aims
We analyzed antibodies to native E.coli ASNase (anti-E.coli ASNase IgG/IgM), PEG-ASNase (anti-PEG-ASNase IgG/IgM) and polyethylenglycol (PEG) (anti-PEG IgG and anti-PEG IgM) in serum prior to administration of PEG-ASNase in the HR and PIII blocks and assessed the predictive value for HSR of the antibodies to PEG-ASNase.
Methods
A total of 563 samples from 202 patients were analyzed. 46 patients developed HSR (CTCAE grade ≥1) to PEG-ASNase (14 patients in HR1, 27 patients in HR2, 5 patients in HR3 and none in PIII).
Results
In each HR block pre-existing anti-PEG-IgG, anti-PEG-IgM, anti-PEG-ASNase-IgG/IgM or anti-E.coli-ASNase-IgG/IgM significantly increased the risk of HSR to PEG-ASNase (p<0.05, Fisher test). No HSRs were observed in the PIII blocks, which coincided with an overall low prevalence of pre-existing antibodies (1-4.5%) compared to the HR blocks where the prevalence was 13-26%.
The areas under the receiver operating characteristic (ROC) curve regarding the predictive accuracy of pre-existing antibodies for subsequent HSR to PEG-ASNase (Table 1) showed high predictivity of pre-existing antibodies for HSR in HR2. Among the four antibodies, pre-existing anti-PEG IgG predicted HRS with the highest sensitivity (true positive rate: 80 % for HR1 and HR3 and 100 % for HR2) and specificity (true negative rate: of 94 %, 96 % and 98 % for HR1, HR2 and HR3, respectively).
Table 1: Areas under the receiver operating characteristic (ROC) curves for pre-existing antibodies and HSR in HR blocks. The closer the AUC is to 1, the higher the predictive accuracy of a test.
HSR to PEG-ASNase in | |||
pre-existing antibody | HR1 | HR2 | HR3 |
anti-E.coli ASNase IgG/IgM | 0.63 | 0.78 | 0.89 |
anti-PEG-ASNase IgG/IgM | 0.63 | 0.92 | 0.80 |
anti-PEG IgG | 0.87 | 0.98 | 0.89 |
anti-PEG IgM | 0.82 | 0.97 | 0.78 |
Conclusion
In the AIEOP-BFM ALL 2009 study, we observed a highly accurate predictivity of anti-PEG IgG antibodies for HSR in HR patients. This finding might be useful for future clinical decisions.
1Rizzari C, Moericke A; Conter V, Valsecchi MG, Zimmermann M, Silvestri D et al. Incidence of Hypersensitivity Reactions (HSR) Reactions (HSR) to Peg-Asparaginase (PEG-ASP) in 6136 Patients Treated in the AIEOP-BFM ALL 2009 Study Protocol. Blood 2019; 134 (Supplement_1):2589.
Keyword(s): Adverse reaction, ALL, Antibody, Asparaginase
Abstract: EP342
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
In the AIEOP-BFM ALL 2009 study, hypersensitivity reactions (HSR) to pegylated E.coli asparaginase (PEG-ASNase) were most commonly reported in high-risk (HR) patients.1 After induction with 2 doses of PEG-ASNase 2 weeks apart, HR patients - in contrast to standard and intermediate-risk patients - received 3 doses of PEG-ASNase, one in each of the three HR blocks (HR1-3), followed by three additional doses, one in each of the three subsequent PIII blocks (PIII 1-3).
Aims
We analyzed antibodies to native E.coli ASNase (anti-E.coli ASNase IgG/IgM), PEG-ASNase (anti-PEG-ASNase IgG/IgM) and polyethylenglycol (PEG) (anti-PEG IgG and anti-PEG IgM) in serum prior to administration of PEG-ASNase in the HR and PIII blocks and assessed the predictive value for HSR of the antibodies to PEG-ASNase.
Methods
A total of 563 samples from 202 patients were analyzed. 46 patients developed HSR (CTCAE grade ≥1) to PEG-ASNase (14 patients in HR1, 27 patients in HR2, 5 patients in HR3 and none in PIII).
Results
In each HR block pre-existing anti-PEG-IgG, anti-PEG-IgM, anti-PEG-ASNase-IgG/IgM or anti-E.coli-ASNase-IgG/IgM significantly increased the risk of HSR to PEG-ASNase (p<0.05, Fisher test). No HSRs were observed in the PIII blocks, which coincided with an overall low prevalence of pre-existing antibodies (1-4.5%) compared to the HR blocks where the prevalence was 13-26%.
The areas under the receiver operating characteristic (ROC) curve regarding the predictive accuracy of pre-existing antibodies for subsequent HSR to PEG-ASNase (Table 1) showed high predictivity of pre-existing antibodies for HSR in HR2. Among the four antibodies, pre-existing anti-PEG IgG predicted HRS with the highest sensitivity (true positive rate: 80 % for HR1 and HR3 and 100 % for HR2) and specificity (true negative rate: of 94 %, 96 % and 98 % for HR1, HR2 and HR3, respectively).
Table 1: Areas under the receiver operating characteristic (ROC) curves for pre-existing antibodies and HSR in HR blocks. The closer the AUC is to 1, the higher the predictive accuracy of a test.
HSR to PEG-ASNase in | |||
pre-existing antibody | HR1 | HR2 | HR3 |
anti-E.coli ASNase IgG/IgM | 0.63 | 0.78 | 0.89 |
anti-PEG-ASNase IgG/IgM | 0.63 | 0.92 | 0.80 |
anti-PEG IgG | 0.87 | 0.98 | 0.89 |
anti-PEG IgM | 0.82 | 0.97 | 0.78 |
Conclusion
In the AIEOP-BFM ALL 2009 study, we observed a highly accurate predictivity of anti-PEG IgG antibodies for HSR in HR patients. This finding might be useful for future clinical decisions.
1Rizzari C, Moericke A; Conter V, Valsecchi MG, Zimmermann M, Silvestri D et al. Incidence of Hypersensitivity Reactions (HSR) Reactions (HSR) to Peg-Asparaginase (PEG-ASP) in 6136 Patients Treated in the AIEOP-BFM ALL 2009 Study Protocol. Blood 2019; 134 (Supplement_1):2589.
Keyword(s): Adverse reaction, ALL, Antibody, Asparaginase