Blinatomumab

Blinatumomab: a CD19/CD3 bispecific monoclonal antibody designed to redirect T cells towards CD19 positive B-cells including leukemic B-cells, and induces their lysis.

Rationale

The drug recently gained accelerated approval by the FDA for the treatment of relapsed or refractory Philadelphia chromosome-negative pre B-cell ALL. In the phase II trial, forming the basis for this approval, blinatumomab demonstrated significant single-agent activity and induced CR and CR with incomplete recovery of peripheral blood counts (CR/CRi) in 43% of 189 adult patients with relapsed or refractory ALL; the majority of patients reaching CR also attained a negative MRD status (82%) that did not translate into long-term remissions in most cases, with a median overall survival of 9 months.

Additional studies in patients in first CR, but MRD positive, show that blinatumomab can induce high response rates (80% MRD negativity) associated with lasting remissions suggesting a role for blinatumomab in the upfront MRD-positive setting.

Bijwerkingen

Blinatumomab infusion might be followed by early cytokine release that can be associated with a clinical cytokine release syndrome, T-cell expansion, and B-cell depletion. Neurologic toxicities represent a unique toxicity that shares similarities with adverse effects known from other T-cell engaging therapies while the specific pathophysiology is still unknown.

Werkingsmechanisme

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