Activity of blinatumomab in lymphoblastic leukemia with impaired T-cell immunity due to congenital immunodeficiency

Abstract

Blinatumomab, a single-chain, bispecific, T-cell–engaging antibody targeting CD19, is effective in B-precursor acute lymphoblastic leukemia (BCP-ALL), even in the context of chemotherapy-related partial T-cell immunodeficiency. We report 2 patients with BCP-ALL and congenital T-cell immunodeficiency, who obtained an excellent response to blinatumomab. The first, a 6-year-old girl with Schimke immuno-osseous dysplasia (SIOD) and combined immunodeficiency disorder (CID) obtained a minimum residual disease–negative (MRD−) remission of high hyperdiploid BCP-ALL with blinatumomab. At last follow-up, the remission had been sustained for 14 months from diagnosis. The second was a 9-year-old boy with Omenn syndrome and CID who received a mismatched bone marrow transplant from his mother at the age of 4 months and was diagnosed with t(3;11)+ (KMT2A-LARS2) BCP-ALL 9 years after his transplant. He received a 4-drug induction followed by blinatumomab for persistent MRD as a chemotherapy-sparing bridge to transplant and achieved an MRD− remission. T-lymphopenia, whether congenital or acquired, does not compromise the efficacy of blinatumomab.

Low leukemia burden improves blinatumomab efficacy in patients with relapsed/refractory B‐cell acute lymphoblastic leukemia

“…Studies of patients with R/R ALL revealed no difference in responses between those who received preemptive steroid treatment and those who did not 10,29 . It has been postulated that blinatumomab activates and causes secondary expansion of a subset of T cells in the reticuloendothelial system allowing it to exert its therapeutic effect even under lymphopenic conditions 30 …”

“…10,29 It has been postulated that blinatumomab activates and causes secondary expansion of a subset of T cells in the reticuloendothelial system allowing it to exert its therapeutic effect even under lymphopenic conditions. 30 The limitations of this study are those inherent to pooled analysis-the heterogeneity of the clinical and treatment characteristics in the patient population, diversity of definitions used for efficacy outcomes, variable follow-up periods, and differences in laboratory techniques used to measure leukemia burden levels.…”

The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials

“…Ramdeny et al showed that blinatumomab was effective in patients with congenital or acquired T‐cell lymphopenia. This suggests that blinatumomab is able to activate and expand a small fraction of functional T cells 65 . In addition, other findings such as the lower efficacy of blinatumomab on high tumour loads (greater than 50% blasts in the bone marrow) should lead to changes in treatment regimens.…”

“…This suggests that blinatumomab is able to activate and expand a small fraction of functional T cells. 65 In addition, other findings such as the lower efficacy of blinatumomab on high tumour loads (greater than 50% blasts in the bone marrow) should lead to changes in treatment regimens. Reduction therapy would be recommended in such cases.…”

Immunotherapy of Neuroblastoma: Facts and Hopes

“…This architecture enables selective binding and bridging of tumor cells to a T cell and then subsequent activation of the T cell to kill the tumor. Blinatumomab is a bispecific CD19 x CD3 antibody that FDA approved for B-cell acute lymphoblastic leukemia, that can be effective even in the face of lymphopenia or immunedeficiancy (85,86). Multiple analogous or similar constructs are being studied for various solid tumors.…”