Page 352 - Read Online

Page 10 of 12 Sharma et al. Neuroimmunol Neuroinflammation 2018;5:43 I http://dx.doi.org/10.20517/2347-8659.2018.51

found to effectively treat CRS-related complications in clinical trials. Eventually, it was approved by the
FDA for this specific purpose in 2017. It is recommended as the first course of treatment when CRS and
neurological toxicity is confirmed as per the grading criteria discussed previously. Tocilizumab can be
dosed at 8mg/kg IV for CRS or CRES, starting as early as grade 1 toxicity. Siltuximab, an anti-IL-6 chimeric
monoclonal antibody, can also be used instead of tocilizumab in these cases, and is dosed at 11mg/kg IV. If
the patient fails to respond to these drugs and proceeds to grade 2 or higher CRS/CRES, then corticosteroids
may need to be used. Corticosteroids appear to be more effective for patients with neurotoxicity only
without concomitant CRS. Dexamethasone is typically dosed at 10mg IV every 6 h, and continued toxicity
without response to dexamethasone may need to be treated with methylprednisolone. There has been
concern that steroids may impact the inflammatory response that is important for the efficacy of CAR-T
cell treatment and may suppress the function of the tumor-directed T cell therapy since they can suppress
T cells and induce apoptosis of these cells. However, preliminary data at this point demonstrates no clear
[36]
objective difference in response rates . Most management protocols advise considering steroids if patients
are demonstrating grade 2 toxicity without response to tocilizumab or siltuximab [23,31] .

CONCLUSION
CAR-T therapy has had promising results in hematological malignancies and has revolutionized the
immunotherapy field in the last several years. There is a great hope that with the identification of the right
antigens, and with improvements in delivery and safety, CNS malignancies might be successfully treated
with this therapy. Early studies are demonstrating some encouraging results , but larger trials are needed
to fully evaluate this modality in treatment of brain cancer (both primary and secondary). It is critically
important for the providers to understand the principles of this therapy, its mechanism of action and
particularly its neurologic toxicity. While the understanding of neurotoxicity continues to evolve, early
integration of the neurology team in the care of patients receiving CAR-T cell therapy clearly provides
benefit. Immunotherapy is an emerging area in oncology and its use, including the indications for CAR-T,
are likely to expand.

DECLARATIONS
Acknowledgements
The authors would like to thank Mr. Ryan Stemen for designing the graphics for this paper.

Authors’ contributions
Researched literature, wrote the manuscript: Sharma A, De Leon G
Provided content, reviewed the manuscript: Porter A, Grill MF, Rosenthal A, Swanson K
Provided content and figures, reviewed the manuscript: Brown CE
Article concept, literature research, writing and reviewing the manuscript: Mrugala MM

Availability of data and materials
Data available on PubMed and www.clinicaltrials.gov.

Financial support and sponsorship
None.

Conflicts of interest
C. E. Brown receives patent royalties and consulting support from Mustang Bio.

Ethical approval and consent to participate
Not applicable.
Consent for publication