car-t - moffitt · cells shipped fresh for car -t cell manufacture . ... used for the treatment of...

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

Kannan, R., Madden, K., & Andrews, S. (2014). Primer on immuno-oncology and immune response. Clinical Journal of Oncology Nursing, 18(3), 311- 326. 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 B- cell 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.