Download Subrena Powell, RN, BMTCN

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
Day 0: pre CAR-T
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: 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
Mini-Mental State Examination
(MMSE)
Brief quantitative assessment of cognitive impairment
 Examines orientation,
memory, attention,
calculation, language and
praxis.
 Maximum score = 30
 Score of ≤ 23 indicates
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
rd
3
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
Kannan, R., Madden, K., & Andrews, S. (2014). Primer on immuno-oncology
and immune response. Clinical Journal of Oncology Nursing, 18(3), 311326. doi: 10.1188/14.CJON.311-317
References
Kochenderfer, J. N., Dudley, M. E., Kassim, S. H., Somerville, R. P.,
Carpenter, R. O., Stetler-Stevenson, M., ... & Raffeld, M. (2015).
Chemotherapy-refractory diffuse large B-cell lymphoma and indolent Bcell malignancies can be effectively treated with autologous T cells
expressing an anti-CD19 chimeric antigen receptor. Journal of Clinical
Oncology, 33(6), 540-549.
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.