Targeted Therapy With the T-Cell–Engaging Antibody Blinatumomab of Chemotherapy-Refractory Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia Patients Results in High Response Rate and Prolonged Leukemia-Free Survival

Abstract

Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.

A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19+tumor cells

“…In the population-variability study, the cytokine release (IL-2, IL-6, TNF, and IFN-g) induced by AFM11 in unfractionated PBMC is reduced relative to that induced by OKT3 across all of the cytokines, and only AFM11-induced IL-6 release approaches that of OKT3; this is consistent with the blinatumomab clinical experience. 32 In unstimulated PBMC spiked with CD19 C tumor cells at a ratio of 5:1, AFM11 induces a dose-responsive cytokine release consistent with its mode of action. Lastly, in the biodistribution study radiolabeled AFM11 exhibited excellent localization to tumor tissue with minimal distribution to normal tissue, excepting the spleen as expected.…”

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

“…Indeed, convincing data to extrapolate a benefit of additional pre-HCT therapy may come from a phase 2 trial with blinatumomab, a bispecific single-chain Ab targeting CD19, in patients with B-lineage ALL having chemotherapy-refractory MRD. 81 In this study, 16 out of 20 MRD þ patients became MRD À after treatment with blinatumomab, and none of the 8 patients subsequently undergoing AlloHCT experienced post-HCT relapse. Although not all patients were responsive to Ab therapy, this finding suggests that elimination of MRD with blinatumomab may improve post-HCT outcomes of patients that otherwise would have been MRD þ at transplantation, but larger studies will be required to conclusively test this possibility.…”

Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment

“…T cells responding to infection expand, then contract; recovery after contraction was the basis for the selection of the dosing holiday 70. The primary endpoint, MRD‐negativity, was achieved in 16 of 20 (80%) evaluable subjects (one subject experienced a Grade 3 seizure and was not evaluable) 71. At a median follow‐up of 33 months, hematologic relapse‐free survival was 60% 72.…”