CAR-T
Subrena Powell RN, MSN, BMTCN®
Objectives Discuss the treatment timeline of a patient
receiving CAR-T therapy
Describe the side effects and management of symptoms of CAR-T therapy
Treatment Schema
CASE STUDY
Patient is a 27 year old male diagnosed with ALL No response to prior treatment of Hyper CVAD
1st Stop: BMT Clinic and Treatment Center
BMT Clinic & Treatment Center
Vital organ testing
Enrolled in CAR-T trial
Education from a Transplant Nurse Coordinator
Line Placement and Leukapheresis
Cells shipped fresh for CAR-T cell manufacture
Conditioning Chemotherapy
Fludarabine 25mg/m2 on Days -4,-3,-2
Cyclophosphamide 900mg/m2 on Day -2 Mesna 300mg/m2 on Day -2 Hourly voids
Palonestron 0.25mg IV on Days -4 and -2
2nd Stop: BMT Inpatient Unit
Admission Admission on Day -1 to the Immune Cell Therapy (ICE-T)
Service
ICE-T Care Team: ICE-T Attending Physician
ICE-T designated Advance Practice Provider (APP)
An assigned inpatient nurse educated on ICE-T trials
Case manager, Dietary, PT/OT, ID, Neurology, etc.
Clinical Trial coordinator
Assessment
Hematology: WBC: 0.30, Hgb: 8.5, Plt: 35, ANC: 200
Neurological: Patient Alert and Oriented, MMSE: 30/30
Respiratory: Room Air
Cardiovascular: Within normal range
Day 0: pre CAR-T
Day 0: CAR-T Infusion Infusion
Normal saline given prior to infusion of cells
Pre-medication with Tylenol and Benadryl
Infusion of Cells
Post infusion normal saline
Then monitor V/S during and q3 hours post transfusion
Neurological Toxicities Patients are at risk for neurotoxicity's associated with
CAR-T infusion/Cytokine Release Syndrome
Prophylaxis/Monitoring includes:
Keppra 1000mg BID started prior to infusion for seizure prophylaxis
Neuro checks q4h & PRN
Mini Mental Status Examination (MMSE) by providers on: Day 0 Day 1 Then every other day and PRN
Examines orientation,
memory, attention, calculation, language and praxis.
Maximum score = 30 Score of ≤ 23 indicates
cognitive impairment
Mini-Mental State Examination (MMSE)
Brief quantitative assessment of cognitive impairment
Cytokine Release Syndrome (CRS)
Serious complication which may occur after infusion of CAR-T cells
Cytokines and chemokines are released by the activated
CAR-T cells and produce a systemic inflammatory response,
similar to that found in severe infection
IL-6
IFN-gamma
Close monitoring by nursing staff is essential
CRS Clinical Features
(Brudno & Kochenderfer, 2016).
Day +1 Assessment
Hematology: WBC: 0.19, Hgb: 6.3, Plt: 40, ANC: <500 Neurological: Alert, oriented, able to participate in care MMSE: 26/30
Respiratory: Room Air Cardiovascular: Normotensive
Daily Events Patient became febrile, Tmax: 39.3º C Blood Cultures completed Chest X-Ray completed (-) Antibiotics started within an hour of fever
Day +2 Assessment
Hematology: WBC: 0.21, Hgb: 8.0, Plt: 43, ANC: <500 Neurological: Alert, oriented, able to participate in care Respiratory: Room Air Cardiovascular: Normotensive
Daily Events Patient remains febrile, Tmax: 39º C
Day +3 Assessment
Hematology: WBC: 0.15, Hgb: 7.6, Plt: 43, ANC: <500 Neurological: Alert, oriented, able to participate in care MMSE: 26/30
Respiratory: Room Air Cardiovascular: Normotensive
Daily Events Patient remains febrile, Tmax: 40.5º C Cultures negative to date
Day +4 Assessment
Hematology: WBC: 0.10, Hgb: 7.5, Plt: 32, ANC: <500 Neurological: Alert, oriented, able to participate in care Respiratory: Room air Cardiovascular: Normotensive
Daily Events Patient remains febrile, Tmax: 40.3º C Cultures negative to date
Day +5: Early Morning 0000: Alert, oriented, still febrile, Tmax 40.5º C
0300: Became obtunded Episode of emesis Could no longer verbally communicate Able to track with eyes, but no motor strength
0600: Seizure-like activity noted Foaming at the mouth Jaw Clenching Upturned Eyes Given Ativan 2mg IV – some improvement noted
Day +5: Afternoon Assessment
Hematology: WBC: 0.14, Hgb: 6.8, Plt: 37, ANC: <500 Neurological: Rapid mental status changes prompted ICE-T provider to order:
Dexamethasone 10 mg IV q6hrs Tocilizumab 8mg/kg IV x1 Neurology consulted for worsening neurotoxicity's
EEG completed (-) MRI ordered: Not completed, possible V-Tach while in MRI machine, test stopped
Respiratory: Pulmonary Critical Care consulted Increasingly tachypnea, RR 30-40s At 1400: Intubation to protect airway r/t to neurological state and body composition
Cardiovascular: Patient increasingly tachycardic, HR 140s, B/P stable
EKG: Sinus Tachycardia Cardiac Enzymes (-)
***Patient transferred to ICU***
Tocilizumab (Actemra) Humanized monoclonal antibody against the
Interleukin‐6 (IL‐6) receptor
Works by blocking the activity of IL‐6, a substance in the body that causes inflammation
Used for the treatment of CRS after CAR-T cell therapy
Day +6 Assessment
Hematology: WBC: 0.22, Hgb: 8.3, Plt: 33, ANC: 130
Neurological: Grade 3 Neurotoxicity No more seizure activity noted MRI performed: small infarct in right inferior cerebellum Dexamethasone 10 mg IV q6hrs
Respiratory: Remains intubated Sedation: Propofol/Fentanyl
Cardiovascular: Patient remains normotensive
Day +7 Assessment
Hematology: WBC: 0.21, Hbg: 6.6, Plt: 23, ANC: 110
Neurological: No seizure activity noted Patient on Dexamethasone 20 mg q12 Per Neurology: MRI findings would not explain CNS changes
Respiratory:
Patient remains intubated and sedated Weaning sedation: opens eyes but otherwise no motor response
Cardiovascular:
Patient remains in NSR, heart rate within normal range
Day +8 Assessment
Hematology: WBC: 0.43, Hgb: 8.8, Plt: 38, ANC: 120
Neurological: Patient on Dexamethasone 20mg q12
Respiratory: Extubated @ 1100 On O2 NC @ 2L
Cardiovascular: Remains in NSR, heart rate within normal range ECHO (-)
Day +9 Assessment
Hematology: WBC: 0.54, Hgb: 9.0, Plt: 56, ANC: 120
Neurological: Afebrile, Cultures negative Patient on Dexamethasone 20mg q24 Patient neurologically intact MMSE: 21/30
Respiratory: Room Air
Cardiovascular: Remains in NSR, heart rate within normal range
***Patient transferred back to BMT Unit***
Day +10 Assessment
Hematology: WBC: 0.45, Hgb: 8.8, Plt: 68, ANC: 150
Neurological: Neurologically intact Afebrile, Cultures negative Dexamethasone discontinued Keppra continued
Respiratory: Room Air
Cardiovascular: Remains in NSR, heart rate within normal range
Day +11 – Day +14 Assessment
Hematology: Day +14: WBC: 1.01, Hgb: 9.7, Plt: 71, ANC: 910
Neurological: Patient neurologically intact Afebrile, Cultures negative Keppra continued
Respiratory: Room Air
Cardiovascular: Remains in NSR, heart rate within normal
range
Day +15: Discharge Assessment
Hematology: WBC: 1.35, Hgb: 9.4, Plt: 65, ANC: 1010 Bone Marrow Biopsy: No morphological evidence of residual B
lymphoblastic leukemia
Neurological: Alert, oriented, following commands MMSE 23/30
Respiratory: Room air
Cardiovascular: Remains in NSR, heart rate within normal range
PT/OT:
Recommendation: Home independently
3rd Stop: BMT Clinic and Treatment Center
Outpatient Follow Up
Patient is monitored with daily labs in BMT Treatment Center following discharge
Once patient becomes more stable they are seen less frequently
Patient recovers and is discharged back to their primary oncologist
Plan Post CAR-T is to bridge to allograft once counts are recovered and donor is found
References Balch, C. M., Fox, B. A., & Kaufman, H. L. (Eds.). (2015). Patient resource cancer guide: Understanding cancer immunotherapy (2nd ed.). Overland Park, KS: Patient Resource.
Brudno, J. N. & Kochenderfer, J. N. (2016). Toxicities of chimeric antigen receptor Tcells: Recognition and management. Blood, 127, 3321-3330. doi: 10.1182/blood-2016-04-703751
Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., … & Brentjens, R. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine, 6(224), 1-10. doi: 10.1126/scitranslmed.3008226
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Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124(2), 188-195. doi: 10.1182/blood-2014-05-552729
Tombaugh, T. N., & McIntyre, N. J. (1992). The mini-mental state examination: A comprehensive review. Journal of the American Geriatrics Society, 40(9), 922-935.