Cancer Care Program - Staff and Physicians

CRS and ICANS Management

• Two specific toxicities unique to CAR T-cell treatment are:
  • Cytokine-release syndrome (CRS)
  • Immune Effector Cell associated neurotoxicity syndrome (ICANS)
• Prompt recognition and urgent aggressive intervention for management of CRS/ICANS are key elements for successful outcomes and lead to shorter ICU stays.
• Almost all CRS/ICANS are reversible with adequate and timely supportive measures.
• Deteriorations in patients’ status are quick and dramatic; as such there is no place for IMCU in the management plan.
• Higher grades of CRS are characterized by rapidly progressive capillary leak syndrome/vasoplegic shock. One fluid bolus is a trigger for ICU involvement.
• Managing persistent hypotension with overt fluid management leads to inferior results versus early pressors.
• Patients in the ICU will be managed by the ICU team. The Bone Marrow Transplant service will assist through consultation.
• Features of multi-organ dysfunction may persist for days or weeks after resolution of CRS. It is essential to continue support during this time.
• Supportive care is the mainstay of ICANS management.
• Indications for ICU admission are outlined below. Transfer will take place ideally within 90 minutes following initial consultation.
• Patients’ outcomes will be reviewed periodically between BMT and ICU teams.

Indications for ICU admission for patients with CRS and/or ICANS

• SBP < 90 mmHg or MAP < 65 mmHg refractory to IV fluid challenge (if a patient requires more than 1000 ml isotonic Crystalloid fluid bolus in a 6 hr period) requiring vasopressors; OR
• Hypoxia/respiratory distress with increasing oxygen requirement (≥ 6L O2/min) or need for ventilatory support; OR
• Clinically significant arrhythmias or acute coronary syndrome with positive troponin; OR
• ICE-Test ≤ 6 points, signs of raised ICP or seizures; OR
• Team concern particularly for high-risk patients

High-risk patients for severe CRS and ICANS

• Older age (≥65 yr)
• Early onset CRS (<24 hr)
• Coexisting comorbid conditions (e.g renal, CVS) High tumor burden
• High pretreatment LDH
• High pretreatment inflammatory markers (ferritin, CRP)

General management guidelines in ICU

• The use of tocilizumab and/or steroids will be in close consultation with the transplant team to avoid jeopardizing T cells function
• Supportive management of organ toxicities as per standard guidelines
• Assess for infection (blood/urine cultures, chest x-ray, ICANS: lumbar puncture, and start empiric antibiotic therapy if not already started
• Laboratory: Crea, Urea, LFTs, WBC, LDH, Ferritin and CRP daily until 72hrs after symptom improvement
• In ICU the ICE score completed by the ICU registered nurse
• In ICU the ICANS assessment is completed by cell therapy physician / physician delegate.
• CRS grading completed by cell therapy physician / physician delegate.
• Consider formal echocardiography (recommended for prolonged severe CRS >72h)
• ICANS: CT/MRI, EEG, neuroprotective care, consider ICP monitoring
• Neurology team will be closely following patients with ICANS

Patients are treated with curative intent. Goals of care discussions will be in consultation with the transplant team

Reproduced with permission from the NCCN Guidelines® for Management of Immunotherapy-Related Toxicities V.1.2022. © 2022 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Reproduced with permission from the NCCN Guidelines® for Management of Immunotherapy-Related Toxicities V.1.2022. © 2022 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Reproduced with permission from the NCCN Guidelines® for Management of Immunotherapy-Related Toxicities V.1.2022. © 2022 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Reproduced with permission from the NCCN Guidelines® for Management of Immunotherapy-Related Toxicities V.1.2022. © 2022 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

• MDACC developed app for guidance on grading and management of CRS and ICANS
  • https://apps.apple.com/us/app/cartox/id1464005828
• CAR T-cell therapy and critical care: A survival guide for medical emergency teams, Messmer et al. Wien Klin Wochenschr. 2021 Dec;133(23- 24):1318-1325.
• Chimeric antigen receptor T-cell therapy — assessment and management of toxicities. Neelapu et al.
  • https://www.nature.com/articles/nrclinonc.2017.148

• Thompson, J. A., Schneider, B. J., Brahmer, J., Achufusi, A., Armand, P., Berkenstock, M. K., Bhatia, S., Budde, L. E., Chokshi, S., Davies, M., Elshoury, A., Gesthalter, Y., Hegde, A., Jain, M., Kaffenberger, B. H., Lechner, M. G., Li, T., Marr, A., McGettigan, S., … Hang, L. (2022). Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN, 20(4), 387–405. https://doi.org/10.6004/jnccn.2022.0020