Approval Status: Approved September 2017
Specific Treatments: CAR T-cell induced Cytokine Release Syndrome
Actemra (tocilizumab) is a humanized anti IL-6 receptor monoclonal antibody and binds specifically to IL-6 receptors. IL-6 is a pro-inflammatory cytokine.
Actemra is specifically indicated for adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome.
Actemra is supplied as a solution for intravenous infusion. The recommended dose for the treatment of CRS given as a 60-minute intravenous infusion is:
- Patients less than 30 kg weight: 12 mg per kg
- Patients at or above 30 kg weight: 8 mg per kg
If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, up to 3 additional doses of Actemra may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CRS patients.
The FDA approval of Actemra for CAR T cell-induced CRS was based on a retrospective analysis of pooled outcome data from clinical trials of CAR T cell therapies for blood cancers, which assessed the efficacy of Actemra in the treatment of CRS. The study population included 45 pediatric and adult patients treated with Actemra, with or without additional high-dose corticosteroids, for severe or life-threatening CRS. Thirty-one patients (69%; 95% CI: 53%–82%) achieved a response, defined as resolution of CRS within 14 days of the first dose of Actemra, no more than two doses of Actemra were needed, and no drugs other than Actemra and corticosteroids were used for treatment. No adverse reactions related to Actemra were reported. A second study confirmed resolution of CRS within 14 days using an independent cohort that included 15 patients with CAR T cell-induced CRS.
Adverse effects associated with the use of Actemra may include, but are not limited to, the following:
- upper respiratory tract infections
- increased ALT
- injection site reactions
The Actemra drug label comes with a boxed warning addressing the potential risk of serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections, which have occurred in patients receiving Actemra.
Mechanism of Action
Actemra (tocilizumab) is a humanized anti IL-6 receptor monoclonal antibody and binds specifically to IL-6 receptors. IL-6 is a pro-inflammatory cytokine. Tocilizumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors.
For additional information regarding Actemra or CAR T-cell induced Cytokine Release Syndrome, please visit https://www.actemra.com/