Poster Abstract
Objectives
Blinatumomab is a bispecific T-cell engager (BiTE) that binds to CD3 on T-cells and CD19 on B-cells. It has been approved for use in Acute lymphoblastic leukemia (ALL) with a regimen that requires constant infusion for four weeks per treatment cycle [1-4]. Recently, there have been studies investigating dose-response after subcutaneous dosing [5, 6] and whether this more convenient method of delivery would have a similar efficacy/safety profile as continuous infusion. It has been hypothesized that BiTEs derive their efficacy by forming trimers between T-cells and malignant cells [7]. In this work, a model-based investigation compares the trimer formation between the two delivery methods.
Methods
We constructed a mechanistic PKPD model of ALL that describes blinatumomab PK in circulation, bone marrow, and periphery, engagement with T-cells and normal and malignant B-cells, and the amount of trimers the drug forms at different dosing regimens.
Results
By simulating various potential subcutaneous dosing regimens, we identify conditions where trimer formation dynamics are similar between constant infusion and subcutaneous dosing when accounting for cell death resulting from the trimer formation.
Conclusions
Based on the model, subcutaneous dosing is a viable and convenient strategy for blinatumomab and is projected to result in similar trimer numbers as constant infusion.
References
[1] BLINCYTO (blinatumomab) [package insert], Thousand Oaks, CA, Amgen Inc., 2022
[2] Goebeler M-E, et al. J Clin Oncol. 2016; 34:1104-1111
[3] Viardot A, et al. Blood. 2016; 127:1410-1416
[4] Katz DA, et al. Blood. 2019; 134(Suppl 1):4077
[5] Martinez-Sanchez et al. Safety and Efficacy of Subcutaneous (SC) Blinatumomab for the Treatment of Adults with Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) [poster], American Society Of Hematology Annual Meeting, 2021
[6] Rossi et al., A Phase 1b Study of Blinatumomab Including Subcutaneous Administration in Relapsed / Refractory (R/R) Indolent Non Hodgkin’s Lymphoma (NHL) [poster], American Society Of Hematology Annual Meeting, 2021