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Randomized Controlled Trial
. 2020 Dec 17;136(25):2955-2958.
doi: 10.1182/blood.2020006214.

Dosing-related saturation of toxicity and accelerated drug clearance with pegaspargase treatment

Yiwei Liu  1 , John C Panetta  1 , Wenjian Yang  1 , Seth E Karol  2 , Cheng Cheng  3 , Jun J Yang  1 , William E Evans  1 , Hiroto Inaba  2 , Ching-Hon Pui  2 , Sima Jeha  2 , Mary V Relling  1
Affiliations
Randomized Controlled Trial

Dosing-related saturation of toxicity and accelerated drug clearance with pegaspargase treatment

Yiwei Liu et al. Blood. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: M.V.R., H.I., C.-H.P., and St. Jude Children’s Research Hospital receive investigator-initiated research funding from Servier Pharmaceuticals. C.-H.P. also received an honorarium from Servier Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Individual post hoc pegaspargase pharmacokinetic estimates day 14 activity, threshold time, Vmax , and CLint during continuation week 7 and week 17 differed by risk arm and randomized pegaspargase dosage levels. There were 84, 89, 82, and 96 patients in low risk (LR, intermittent dosing) 2500 U/m2, standard/high risk (SHR, continuous dosing) 2500 U/m2, LR 3500 U/m2, and SHR 3500 U/m2 group, respectively, for week 7; and 63, 74, 66, and 79 in LR 2500, SHR 2500, LR 3500, and SHR 3500 group, respectively, for week 17. In each plot, red P values compare between different randomized dosage levels within SHR patients; blue P values compare between different randomized dosage levels within LR patients. P values below each plot in black compare between different risk arms randomized to receive the same dosage level. All P values were generated using linear mixed-effect model adjusting for antibody status and clinical reaction. Only randomized patients were included in these analyses.
Figure 2.
Figure 2.
Randomization to 2500 vs 3500 U/m2 pegaspargase dosage did not affect incidence of pancreatitis, thrombosis, osteonecrosis, and serious hepatotoxicity. (A) Grade ≥2. (B) Grade ≥2. (C) Grade ≥2. (D) Grade ≥3. Green lines are standard/high risk (SHR) patients randomized to receive pegaspargase 2500 U/m2 (n = 117), red lines are SHR patients randomized to receive pegaspargase 3500 U/m2 (n = 116), blue lines are low risk (LR) patients randomized to receive pegaspargase 2500 U/m2 (n = 88), purple lines are LR patients randomized to receive pegaspargase 3500 U/m2 (n = 90). Red P values compare between SHR 2500 U/m2 and SHR 3500 U/m2 patients. Blue P values compare between LR 2500 U/m2 and LR 3500 U/m2 patients. Percentage values show the cumulative incidence of the corresponding toxicity in each risk/dosage group. Only randomized patients were included in these analyses.
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References

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