Early use of tocilizumab and lead-in dose to mitigate flotetuzumab associated infusion-related reaction/cytokine release reaction in patients with relapsed or refractory acute myeloid leukemia

Flotetuzumab, an investigational CD123 x CD3 DART protein, is designed to target acute myeloid leukemia (AML) cells by co-engagement of a CD123 and CD3 expressing T cells as effector cells. The dose-dependent T-cell activation and concomitant cytokine release, including interleukin 6 (IL-6), is associated with antileukemic activity and cytokine release syndrome (CRS), significant treatment-related toxicity. CRS manifests as chills/rigors, fever, dyspnea, hypotension, hypoxia, and tachycardia. During the clinical development of flotetuzumab, notable strategies adopted to mitigate the incidence and severity of CRS events include early use of tocilizumab (8 mg/kg IV), IL-6 receptor antagonist, and “priming” with MS LID dosing regimen, resulting in decreased incidence and severity of IRR/CRS events leading to greater tolerability of the target dose of 500 ng/kg/day with fewer dose interruptions or discontinuation of flotetuzumab infusion.

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