Luis Álvarez-Vallina
Head of the Clinical Research Unit in Cancer Immunotherapy at CNIO-HMarBCN
This is a phase II, international, multicentre, prospective, prospective, well-designed clinical study of remarkable quality.
This work reaffirms the enormous potential of bispecific antibodies, and in particular of a type of bispecific antibody that recognises a tumour antigen and an activating molecule on the T lymphocyte. This type of bispecific T cell engager (TCE) antibody leads to the activation and proliferation of T lymphocytes, with the consequent release of cytokines and activation of cytotoxic functions.
The antibody used in this clinical trial (blinatumomab) is a small molecule called BiTE (Bispecific T cell Engager) that is designed to interact with CD19 on B cells and CD3 on T cells, and due to its compact structure is very efficient in the formation of conjugates between leukaemic cells and T cells. Blinatumomab was the first bispecific antibody approved for the treatment of haematological cancers. In December 2014, the US Food and Drug Administration (FDA) approved its clinical use in patients with relapsed or refractory B-cell acute lymphoid leukaemia (ALL).
This study demonstrates the potential of blinatumomab in patients younger than 1 year with newly diagnosed CD19+ B-precursor ALL with rearranged KLMT2A, a highly aggressive disease with a 3-year event-free survival of less than 40%. The bispecific antibody is applied in a 28-day cycle, and the study design was based on two hypotheses: that blinatumomab treatment should be applied early in treatment, and immediately after induction therapy to reduce the incidence of side effects and toxicity.
The follow-up period is short, but the clinical results are spectacular, with a 2-year disease-free survival of 81.6%, compared to 49.4% for conventional therapy.
Blinatumomab has demonstrated efficacy in different types of B malignancies since its initial approval in 2014. This work demonstrates the potential of bispecific antibodies in a type of paediatric leukaemia with a very poor prognosis, but in my opinion reaffirms the therapeutic validity of "T-redirection" strategies, which are the basis of the next revolution in cancer immunotherapy.