Grade

Blinatumomab

Two PK studies in children have been published. No effect of age on the PK of blinatumomab has been found. However, the PK behavior of antibodies in infants is known.

Level 1

Population PK model including infants

Author	Method	Number of Patients/Infants(<1yrs)	Age(yr), Median(range)	Age related findings
Clements (2020)	One compartment popPK model.BSA was included as covariate on CL.	674 / >2 (Fig. 1b)	41.0 (0.6-80)	No effect of age on BSA-normalized CL (L/h/m²). Dosing should be based on BSA in younger patients.

Level 3

Non-compartmental PK study or PK model without infants

Author	Method	Number of Patients/Infants(<1yrs)	Age(yr), Median(range)	Age related findings
Von Stackelberg (2016)	Non-compartmental pharmacokinetics	49 / NS - Phase I,44 / NS - Phase II	6 (<1-16) - Phase I, 10.5 (<1-17) -Phase II	Pharmacokinetics consistent between age groups.

Table 1

Table 1 Model derived dosing nomogram for busulfan to achieve a target total AUCday0-4 of 90 mg/L*h (obtained from Bartelink et al. Clin Pharmacokinet; 2012:51: 331-345)

BW(kg)	Dose (mg/kg/day)
3	3.8
5	4.7
7	5.1
8-13	5.2
15-16	5.1

Figure 3

Figure 3 Vincristine exposure (AUC) values observed in neonate and infant patients following doses of >0.05mg/kg and doses of ≥0.05mg/kg, as compared to exposures observed in older children receiving a dose of 1.5mg/m2 (**** p <0.0001). Blue dashed lines indicate proposed therapeutic window.