care™community allied health car-t primer
TRANSCRIPT
CARE™ Community Allied Health
CAR-T Primer Adrianna Alyssa DeCastro, BScN, RN
Stronach Regional Cancer Centre at Southlake
Learning Objectives
§ What is CAR T-cell therapy?
§ Learn the different “steps” of the CAR T process
§ Understand what patients are candidates for CAR T-Cell Therapy (CAR T)
§ Understand and describe CAR T to patients
§ Understand roles of referral/transplant Centres pre- and post- CAR T
Locke & Neelapu et al AACR 2017 #9986
§ CAR T-cell therapy is a cellular therapy using a patient’s own immune system cells to fight cancer
§ They’re made by removing T-lymphocytes from the patient, modifying them in a lab to intensify the immune system’s natural response to cancer, and re-injecting them into the patient
§ CAR T cells are a form of cellular therapy that has produced exceptional results in some patients and is being tested against a variety of different cancer types.
§ This video will explain CAR T-cell therapy:
https://youtu.be/OadAW99s4Ik
What is CAR T-cell therapy?
Stages of the CAR T-Cell Therapy Process
Consult andwork-up
Apheresis
Bridging therapy
Lymphodepleting chemotherapy
CAR T-cell infusion
AE monitoring
Long-term follow up
All of these are opportunities for nurses to educate patients and caregivers
Multidisciplinary Approach to CAR T-Cell Therapy
MDs/APPs
Pharmacists
Cellular therapy
ICU
Infectious disease
Patient
Slide credit: clinicaloptions.com
Neurology
Social workers RNs
Coordinators
Educators
Infusion
InpatientICU
Referring providerand staff
Multidisciplinary Roles for Delivering CAR T Cell Therapies
§ Non-CAR MDs§ Administrative staff§ Nursing
INTAKE CONSULTATION COLLECTION BRIDGING INFUSION EARLY CARE LATE CARE
§ CAR-certified MDs§ Nurse coordinator§ Social worker§ Apheresis staff
§ Cell therapy/donor room§ Laboratory medicine§ Nurse coordinator§ Manufacturers, FACT
§ Non-CAR MDs§ CAR MDs§ Nursing
§ CAR MDs§ Cell therapy§ Nursing§ Pharmacy§ FACT
§ CAR MDs§ ICU, neurology§ Nursing§ Pharmacy
§ CAR MDs§ Non-CAR MDs§ Nursing
§ Nurses have an important role in patient and caregiver education and supporting BOTH identification and referral of candidates
§ Steps and Required Personnel for CAR T-Cell Program:
Consult and work-up–includes identifying appropriate patients
7
Consult andwork-up
Apheresis
Bridging therapy
Lymphodepleting chemotherapy
CAR T-cell infusion
AE monitoring
Long-term follow up
Stages of CAR T-cell procedure
Locke & Neelapu et al AACR 2017 #9986
§ This is an evolving area….
§ In Canada public CAR T-cell therapy is available for‒ Relapsed ALL
‒ Relapsed aggressive B-cell NHL (DLBCL) after 2 therapies **
‒ Includes relapse after autologous stem cell transplant (ASCT)
‒ Includes patients who may not have been candidates for ASCT
‒ Older patients (historically over 70 years were not considered ASCT candidates)
§ Specifics for each patient with relapsed DLBCL should be discussed directly with CAR T-cell site
Who are candidates for CAR T-cell procedure?
Locke & Neelapu et al AACR 2017 #9986
CAR T-cell for ALL in Adults - MD Anderson (NEJM 2018)
CR rate: 83%
Median EFS: 6.1 mo
Median OS: 12.9 mo
N= 53 patients
N Engl J Med 2018; 378:449-459
CD19 has been the target for the first CARTs
CD19 antigen on lymphoma and ALL cells is target for CAR T-cells
CD19 CAR T Therapies in B-Cell Lymphomas
Therapy Indications:
Tisagenlecleucel*
§ Adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy, including:o DLBCL Not Otherwise Specified (NOS)o DLBCL arising from follicular lymphoma (FL)o High-grade B-cell lymphoma
Axicabtageneciloleucel*
§ Adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy, including:o DLBCL NOSo DLBCL arising from FLo Primary mediastinal large B-cell lymphoma (PMBCL)o High-grade B-cell lymphoma
Lisocabtagenemaraleucel
§ Adults with R/R large B-cell lymphoma including:o Relapsed/Refractory DLBCLo PMBCLo FL grade 3Bo Mantle Cell Lymphoma
Three major anti-CD19 CAR T cell products for B-Cell Lymphomas
*Health Canada Approved
StudyTRANSCEND 001-Lisocabtagenemaraleucel
ZUMA1 –Axicabtageneciloleucel (Axi Cel)
JULIET-Tisagenlecleucel
Reference Abramson et al. ASCO 2018
Neelapu et al. NEJM 2017Locke et al. Lancet Oncol 2019 Schuster et al. NEJM 2019
CAR T dose 0.5-1 x 108 2 x 106/kg Up to 1-5 x 108
Conditioning therapy
Cyclophosphamide/ Fludarabine (Cy/Flu) Cy/Flu Cy/Flu or
Bendamustine
Relapsed/Refractory Relapsed or refractory Refractory Relapsed or refractory
Relapse post-ASCT 38% 23% 49%
Bridging therapy Allowed None Allowed
Treated/Enrolled 114/134 (85%) 109/120 (90%) 111/165 (67%)
CD19 CAR T-cell Trials in B-Cell LymphomasAvailable in Canada
Locke & Neelapu et al AACR 2017 #9986Neelapu, Locke, et al, ASH 2019
ZUMA-1: Efficacy of Axi Cel§ Median FU 39.1 Mo§ Median OS 25.8 Mo § 3-year OS rate of 47%
We are curing patients…..
ZUMA-1: Efficacy of Axi Cel
The better the response the longer the duration of remission
JULIET: Efficacy of Tisagenlecleucel
§ ORR: 52%
§ CR rate: 40%
§ 12-month rate of relapse-free survival : 65% all patients, 79% in patients with CR
Schuster. NEJM. 2019;380:45.
OS
0 222018161412108642Mos Since Infusion
1.0
0.8
0.6
0.4
0.2
0
Prob
abili
ty o
f Sur
viva
l
Patients with CR
All patients
Where Does CAR T Fit in Current DLBCL Practice?
First-line/Induction ChemotherapyR-CHOP SOC
HDT/Autologous HSCTSecond-line/Salvage Chemotherapy
R/R (~ 1/3 of patients)
CAR T-Cell Therapy
DLBCL
R/R
Tilly. Ann Oncol. 2015;26 Suppl 5:v116
Key Factors in Determining Candidacy for CAR T-Cell Therapy(Focus on Aggressive B-cell NHL (DLBCL)
Factor Comments/Questions
Indications§ Does the patient have relapsed/refractory B-cell lymphoma after ≥ 2 lines of systemic
therapy? § Does the patient meet the criteria for a clinical trial?
Kinetics of disease progression
§ Would the patient be able to go through leukapheresis (without immediate use of steroids/chemotherapy) and remain stable until the T-cell infusion (3-4 wks)?
§ Does the patient need alternative therapy prior to CAR T-cell therapy consideration?Immediate prior therapy
§ How would this affect the ability to successfully manufacture CAR T-cells (i.e. obtain sufficient numbers of T-cells and expand)?
Concomitant immunosuppressive therapy
§ Can this be safely stopped prior to collection?
Active infection § Higher risk of complications if patient experiences Cytokine Release Syndrome (CRS)
Non-disease related comorbidities
§ i.e. severe cardiac dysfunction, active symptomatic neurologic symptoms § Patients with primary central nervous system (CNS) lymphoma are not candidates.
However, CNS involvement can be treated and eradicated and then the patient may safely move forward
Referral, Eligibility, Consult, and Workup
§ Key information:
‒ Does the patient meet criteria for commercial CAR T-cell product or a CAR T-cell clinical trial?
‒ Do the medical history, physical exam, evaluation of performance status, and baseline laboratory studies demonstrate that it is safe to proceed?
‒ Is a caregiver available 24 hrs/day, 7 days/wk?
‒ What are the local lodging requirements and financial implications?
§ Nurses can:
‒ Review plan for workup and rationale
‒ Review and provide copy of consents in advance for patient and caregiver review
‒ Provide education in verbal and written form
Beaupierre. J Adv Pract Oncol. 2019;10(suppl 3):29.
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
Referral Centres role is identifying and referring appropriate patients
Slide credit: clinicaloptions.com
Guidance for Referral
§ Direct communication with the CAR-T centre early to determine the best timing of potential CAR T-cell therapy referral
§ Maintain clear communication prior to leukapheresis, during bridging chemotherapy, and prior to T-cell infusion to ensure successful collection and manufacturing of T-cells and safe administration
Overview of CAR T-Cell Therapy for Patients
§ WBCs are collected from a patient
§ The cells are sent to a laboratory where T-cells are isolated
§ T-cells are genetically modified to add CAR (chimeric antigen receptor)
§ The modified CAR T-cells are infused back into the patient where they multiply and identify and destroy cancer cells
Jacobson. Blood. 2011;118:4761.
When a patient is identified as being a potential CART candidate they will need education
Leukapheresis (done at transplant centre)
§ Nurses should:‒ Review the procedure
‒ Review the risks and potential adverse events (eg, hypocalcemia)
‒ Review the potential for catheter placement and associated risks
‒ Review medications to identify risk for bleeding and hypotension
‒ Provide a copy of and review the consent for apheresis
§ Leukapheresis time is 4-6 hrs
§ T-cells are labeled, packaged, and shipped to the manufacturing facility
Slide credit: clinicaloptions.comBeaupierre. J Adv Pract Oncol. 2019;10(suppl 3):29.
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
CAR T-Cell Manufacturing
Median manufacturing time: 17-28 days
Patients undergo lymphodepleting (and possibly salvage/bridging) therapy
Majors. EHA 2018. Abstr PS1156. Lim. Cell. 2017;168:724. Sadelain. Nat Rev Cancer. 2003;3:35. Brentjens. Nat Med. 2003;9:279. Park. ASH 2015. Abstr 682. Axicabtagene ciloleucel PI. Tisagenlecleucel PI.
Slide credit: clinicaloptions.com
CD19
Tumor cell
Activity
Viral vector with CAR DNA
CAR-engineered
T-cell
Leukapheresis Manufacturing InfusionCollect patient’s white blood cells
Isolate and activate T-cells
Engineer T-cells with CAR gene
Expand CAR T-cells
Infuse same patient with CAR T cells
Bridging Therapy (Referring site can do)
§ Several weeks may pass between leukapheresis and the administration of CAR T-cells; bridging therapy may be given to patients in order to:
‒ Palliate symptoms
‒ Debulk the primary tumor
‒ Preserve functional status in order to safely administer cells
§ May consist of chemotherapy, steroids, radiation therapy
§ Important to coordinate this therapy with the transplant Centre to assure therapies will not adversely affect T-cell collection or infused T-cells
§ Nurse should provide education focused on:
‒ Rationale for bridging therapy
‒ Importance of appointments for blood work, imaging, and other procedures to monitor patients’ disease state
‒ Symptom management and precautions
‒ When to notify the treatment team
Beaupierre. J Adv Pract Oncol. 2019;10(suppl 3):29.
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
Lymphodepletion (Referring Centre OR Transplant Centre)
§ Goals of lymphodepleting chemotherapy:‒ Deplete regulatory T-cells to
make room for CAR T-cells
‒ Foster in vivo proliferation of infused CAR T-cells
§ Regimens vary: approved product labels recommend fludarabine and cyclophosphamide for adults
§ Nurse education focused on:‒ Central line placement
‒ Location is often ambulatory setting
‒ Home chemotherapy precautions
‒ Caregiver requirements and responsibilities
‒ Local lodging requirement
‒ Symptom management
‒ When and how to notify the treatment team
Beaupierre. J Adv Pract Oncol. 2019;10(suppl 3):29.
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
CAR T-Cell Administration (Transplant Centre)
§ Check patient suitability (central line requirement, vital signs/labs, any signs/symptoms of active infection)
§ Verify product
§ Inpatient or ambulatory setting?
‒ Cell appearance
‒ Premedications
‒ Hydration
‒ Cells are infused at bedside
‒ Provide wallet card
§ Monitor for possible reactions; report new symptoms to the team
§ Reinforce that escalation of care is available if necessary
Slide credit: clinicaloptions.comBeaupierre. J Adv Pract Oncol. 2019;10(suppl 3):29.
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
Nursing Issues:
Posttreatment Monitoring – inpatient and outpatient
§ Adverse event assessments‒ Cytokine-release syndrome‒ Neurotoxicity
§ Count recovery‒ Infection
§ Response to therapy
§ Potential long-term adverse events
Slide credit: clinicaloptions.com
Locke & Neelapu et al AACR 2017 #9986
‒ Cytokine Release Syndrome
‒ Neurotoxicity Syndrome
‒ Tumour Lysis Syndrome
‒ Usual management: supportive care, fluid and electrolyte, rasburicase
§ These occur in most circumstances while patient is admitted and observed after CAR T-cell infusion BUT may be delayed and occur after patient discharged (referral Centres may become involved)
Acute Toxicities with CART therapy(Transplant Centres)
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
Both entities related to cytokines and increased capillary leak of vessels resulting in organ dysfunction
Cytokine-Release Syndrome
§ Typical onset 2-3 days, duration 7-8 days
§ Ranges in severity from low‐grade constitutional symptoms to high‐grade syndrome with life‐threatening multiorgan system failure
§ On a spectrum with macrophage activation syndrome
§ Rarely, severe CRS can evolve into fulminant hemophagocytic lymphohistiocytosis
§ Characterized by high levels of TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-8, and IL-10
§ Correlates with peak T-cell expansion
Lee. Blood. 2014;124:188.Slide credit: clinicaloptions.com
Time Course of Cytokine Changes and Clinical Findings in Grade 3 CRS
30002500200015001000
500500400300200100
0
pg/m
L
CRP mg/L (< 3 m
g/L)
300250200150100100806040200
300 2 4 8 10 12 14 20TocilizumabDay After T-Cell Infusion
Fever
Neurologic symptoms
Vasopressor 2Vasopressor 1
and/or IL-6
IFN-yOtherCRP
Immune Effector Cell–Associated Neurotoxicity Syndrome (Neurotoxicity Syndrome)
§ Typical onset 4-6 days, typical duration 14-17 days
§ Toxic encephalopathy with symptoms of mild headaches, confusion, and delirium; expressive aphasia; occasional seizures; and rarely, cerebral edema
§ Initial findings can be very subtle
‒ Importance of daily cognitive screening
§ Can occur in the presence of absence of systemic CRS
§ Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood–brain barrier permeability
Gust. Cancer Discov. 2017;7:1404. Cancer Discov. 2018;8:4.Slide credit: clinicaloptions.com
First 7-10 days after infusion daily assessment (usually in-patient)
§ Daily lab
‒ CRP, ferritin (increase with CRS)
‒ TLS labs (Ca, PO4, LDH, Cr)
‒ CBC, chem 6, LFTs
§ Bacterial/Fungal prophylaxis as per institution guidelines
§ Clinical assessment
‒ Vitals – fever, hypotension, hypoxia
‒ Mental status
MD Anderson. CAR cell therapy toxicity assessment and management. 2017. Neelapu. Nat Rev Clin Oncol. 2018;15:47.
Nursing Considerations: After CAR T-Cell Infusion
Event Recommendation
CRS
§ Educate patients, caregivers on signs and symptoms§ Take vital signs Q4H and as needed§ Weigh patient daily§ Record intake and output Q4H§ Implement interventions to manage rigors, fevers§ Monitor for signs of tumor lysis syndrome
NT§ Maintain seizure precautions§ Assess neurologic status every shift and as needed§ Initiate neurologic checks as needed
Nursing Standards of Care for Patients Experiencing CRS, Neurologic Toxicities
Halton. Clin J Oncol Nurs. 2017;21(2 suppl):35.
Mental Status Screening in hospital
Lee. Biol Blood Marrow Transplant. 2019;25:625
Time Course of Toxicities With Approved CAR T Therapies
§ CRS: characterized by fever at the onset; symptoms can be progressive and, in addition to fever, may include capillary leak/hypoxia, end organ dysfunction, and hypotension
§ ICANS: toxic encephalopathy with symptoms of mild headaches, confusion, and delirium; expressive aphasia; occasional seizures; and rarely, cerebral edema; can occur in the presence or absence of systemic CRS
Number of Days (Range)
CRS Neurologic AEsMedian Time
to OnsetMedian
DurationMedian Time
to OnsetMedian
Duration*Axicabtageneciloleucel 2 (1-12) 7 (2-58) 4 (1-43) 17
Tisagenlecleucel 3 (1-51) 8 (1-36) 6 (1-359) 14*With tisagenlecleucel, encephalopathy has been observed to last up to 50 days.
1. Axicabtagene ciloleucel PI. 2. Tisagenlecleucel PI. Lee. Blood. 2014;124:188
Safety in CD19 CAR T Trials in Aggressive Lymphoma
Study N CRS All Grades
CRS Grade ≥3
NT All Grades
NT Grade ≥3
Tociusage
Steroid usage
Ref
ZUMA1 108 92% 11% 67% 32% 45% 29% Neelapu et al, NEJM 2017
JULIET 111 58% 22% 21% 12% 15% 11% Schuster et al, NEJM 2019
TRANSCEND 73 37% 1% 25% 15% 17% 21% Abramson et al, ASCO 2018
§ Lee criteria used for CRS grading on ZUMA1 and TRANSCEND
§ U Penn criteria used for CRS grading on JULIET
§ All trials used CTCAE criteria for neurotoxicity (NT) grading
Key acute toxicities: cytokine-release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS)
Principles of Toxicity Management by Grade
§ Always rule out/treat alternative causes
§ If tocilizumab refractory, consider corticosteroids
§ Patients with neurotoxicity should receive AEDs and appropriate CNS imaging, EEG monitoring
§ Steroid dosing for neurotoxicity may vary between products
§ Patients on steroids should receive appropriate fungal prophylaxis
Grade CRS Neurotoxicity CRS + Neurotoxicity1 Supportive care Supportive care Supportive care
2 Tocilizumab Steroids (dexamethasone or methylprednisolone)
Tocilizumab + steroids (dexamethasone)
3 Tocilizumab Steroids (dexamethasone) Tocilizumab + steroids (dexamethasone)
4Tocilizumab + high-
dose steroidsICU/critical care
High-dose steroids (methylprednisolone)
ICU/critical care
Tocilizumab + high-dose steroids
(methylprednisolone) ICU/critical care
MD Anderson. CAR cell therapy toxicity assessment and management. 2017. Neelapu. Nat Rev Clin Oncol. 2018;15:47.
Late Toxicities after CD19 CAR T (Transplant and Referral Centres)
§ Late neurotoxicity events including transient aphasia and seizures have occurred up to 2 months after axi-cel therapy
§ Prolonged >/= grade 3 cytopenias beyond day 30 observed in ~30% of patientsü Managed with growth factors (filgrastim) and transfusions as neededü No patients needed allogeneic SCT
§ B-cell aplasia occurs in almost all patients and can persist >1 year although durable remissions can be seen in patients who recover B cellsü Immunoglobulin replacement therapy used only in patients with both
hypogammaglobulinemia and recurrent infections
• Infections (delayed) occurred in up to 55% of patients in pivotal trials often after discharge from hospital
Sattva Neelapu. CHC 2019; Chimeric Antigen Receptor Cell Therapy for Lymphomas. Accessible at: https://careeducation.ca/events/chc2019/
Consultandwork-up
Apheresis
Bridgingtherapy
Lymphodepletingchemotherapy
CART-cellinfusion
AEmonitoring
Long-termfollowup
Ongoing follow-up at referral Centres for longer term care…
§ Day to day management of longer term complications / issues
‒ “Late onset” tumor lysis, CRS
‒ Transfusion
‒ Infection surveillence
‒ IVIG if needed
§ Critical to maintain good dialogue with Transplant site particularly in early discharge period
§ Nursing often has good contact with transplant coordinators
Summary: CAR T-cell therapy and nursing
§ Nurses need to understand CAR T-cell therapy to support transitions for patients and collaboration between providers
§ Nurses provide patient and caregiver education to facilitate an optimal patient experience
§ Nurses help to coordinate care between referring centers and CAR T-cell treatment centers for the successful management of patients
§ Nurses provide ongoing patient, caregiver, and peer education regarding CAR T-cell therapy
§ Nurses should routinely review and update educational tools as CAR T-cell therapy continues to expand
Questions / Discussion
ASTCT Guidelines for Grading of CRS
Parameter Grade 1 Grade 2 Grade 3 Grade 4Fever Temp ≥ 38°C Temp ≥ 38°C Temp ≥ 38°C Temp ≥ 38°CwithHypotension
None Not requiring vasopressors
Requiring a vasopressor with or without vasopressin
Requiring multiple vasopressors
(excluding vasopressin)
and/orHypoxia None Requiring low-
flow nasal cannula or
blow-by
Requiring high-flow nasal cannula,
facemask, nonrebreather mask,
or Venturi mask
Requiring positive pressure (eg, CPAP, BiPAP, intubation,
and mechanical ventilation)
Lee. Biol Blood Marrow Transplant. 2019;25:625.
New ASTCT Guidelines for Grading of ICANSNeurotoxicity Domain Grade 1 Grade 2 Grade 3 Grade 4
ICE score* 7-9 3-6 0-2 0 (pt is unarousable)
Depressed level of consciousness
Awakens spontane
ously
Awakens to voice
Awakens only to tactile stimulus
Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse;
stupor or coma
Seizure N/A N/A Any clinical seizure focal or generalized that resolves rapidly or nonconvulsive
seizures on EEG that resolve with intervention
Life-threatening prolonged seizure (> 5 mins) or repetitive clinical or electrical seizures without return to baseline in
between
Motor findings N/A N/A N/A Deep focal motor weakness such as hemiparesis or paraparesis
Elevated ICP/cerebral edema
N/A N/A Focal/local edema on neuroimaging
Diffuse cerebral edema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI palsy; or papilledema; or
Cushing’s triad
*See next slide. An ICE score of 0 may be classified as grade 3 ICANS if patient is awake with global aphasia; otherwise classified as grade 4 ICANS if unarousable.
Lee. Biol Blood Marrow Transplant. 2019;25:625.
New ASTCT Guidelines for Grading of ICANS: ICE Score (bedside Screening)
Parameter Score (Points)Orientation: year, month, city, hospital 4Naming: ability to name 3 objects (eg, point to clock, pen, button) 3Following commands: ability to follow simple commands (eg, “show me 2 fingers” or “close your eyes and stick out your tongue”)
1
Writing: ability to write a standard sentence 1Attention: ability to count backwards from 100 by 10 1
3-6, grade 2 ICANS
0-2, grade 3 ICANS
Scoring:
10, no impairment
7-9, grade 1 ICANS
Lee. Biol Blood Marrow Transplant. 2019;25:625.
0 due to patient unarousable and unable to perform ICE assessment, grade 4 ICANS
Pharmacist’s Role in Toxicity Management (Transplant Centre)
§ Undergo training for management of CRS and neurologic toxicities associated with CAR T-cell therapies
§ Ensure availability of toci
• Must have on-site, immediate access
• Must have minimum of 2 doses available for each patient per infusion within 2 hrs after infusion
§ Develop ordering protocols and order sets to ensure timely administration of toci, corticosteroids, and supportive medications as needed for CAR T-cell associated toxicities
Perica. Biol Blood Marrow Transplant. 2018;24:1135.