Dosing & Uses
Dosage Forms & Strengths
injection, suspension
- A single dose contains 50-110 x 106 CAR-positive viable T cells, consisting of CD8 and CD4 components, with each component supplied separately in single-dose vials
- More than 1 vial of each of the CD8 component and/or CD4 component may be needed to achieve the dose
- Each vial contains 6.9-322 x 106 CAR-positive viable T cells in 4.6 mL cell suspension (1.5-70 x 106 T cells/mL)
- Check Rlease for Infusion (RFI) Certificate for specific content
B-Cell Lymphoma
Chimeric antigen receptor (CAR) T-cell immunotherapy (Anti-CD19) indicated for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B
Indications include patients who have
- Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; OR
- Refractory or disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) owing to comorbidities or age; OR
- Relapsed or refractory disease after ≥2 lines of systemic therapy
Lymphodepleting chemotherapy
- One treatment course consists of fludarabine- and cyclophosphamide-lymphodepleting chemotherapy followed by IV infusion of lisocabtagene maraleucel
- Confirm availability of lisocabtagene maraleucel before starting lymphodepleting chemotherapy
- Fludarabine 30 mg/m2 IV plus cyclophosphamide 300 mg/m2 IV qDay for 3 days
- Infuse lisocabtagene maraleucel 2-7 days after completing lymphodepleting chemotherapy
- Delay lisocabtagene maraleucel infusion if patient has unresolved serious adverse events from lymphodepleting chemotherapy, active uncontrolled infection, or active graft-versus-host disease (GVHD)
Premedication
- Premedicate with acetaminophen 650 mg PO and diphenhydramine 25-50 mg PO/IV (or other H1 antihistamine) ~30-60 minutes before CAR T-cell infusion
- Avoid prophylactic use of systemic corticosteroids at all times (may interfere with CAR T-cell activity), except in the case of a life-threatening emergency
Lisocabtagene maraleucel IV infusion
- For autologous use only; administer 2-7 days after completing lymphodepleting chemotherapy
- Dose based on the number of CAR-positive viable T-cells per vial
- After 1 line of therapy: Single dose containing 90-110 x 106 CAR-positive viable T-cells
- After ≥2 lines of therapies: Single dose containing 50-110 x 106 CAR-positive viable T-cells
- Single dose consists of 1:1 CAR-positive viable T-cells of the CD8 and CD4 components
- Each component supplied separately in 1-4 single-dose vials
Dosage Modifications
Cytokine release syndrome (CRS) management
NOTE: If corticosteroids are initiated, continue for at least 3 doses or until complete resolution of symptoms, and consider corticosteroid taper
-
Grade 1
- Symptoms: Fever
- <72 hr after CAR T-cell infusion: Consider tocilizumab 8 mg/kg IV over 1 hr, not to exceed 800 mg; may also consider dexamethasone 10 mg IV q24hr
- ≥72 hr: Treat symptomatically
-
Grade 2
- Symptoms require and respond to moderate intervention; oxygen requirement <40% FiO2 or hypotension responsive to fluids or low dose of one vasopressor or Grade 2 organ toxicity
- Administer tocilizumab 8 mg/kg IV infused over 1 hr; not to exceed 800 mg
- Repeat tocilizumab q8hr as needed if not responsive to IV fluids or increasing supplemental oxygen; not to exceed 3 doses in a 24-hr period or 4 doses in total; after 2 doses of tocilizumab, consider alternant immunosuppressants
- If improving, discontinue tocilizumab
- If <72 hr: Dexamethasone 10 mg IV q12-24hr
- If ≥72 hr: Consider dexamethasone at above dose
- No improvement within 24 hr or rapid progression: Repeat tocilizumab and escalate dose and frequency of dexamethasone (10-20 mg IV q6-12hr); if no improvement on maximized dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed
-
Grade 3
- Symptoms require aggressive intervention; oxygen requirement ≥40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis
- Tocilizumab administration per Grade 2; if improving, discontinue
- Corticosteroid dose as for Grade 2; taper if improving or manage as Grade 2 if not improving
-
Grade 4
- Life-threatening symptoms; requires ventilator support, continuous venovenous hemodialysis, or Grade 4 organ toxicity (excluding transaminitis)
- Tocilizumab administration per Grade 2; if improving, discontinue
- Corticosteroid dose as for Grade 2; taper if improving or manage as Grade 2 if not improving
Neurologic toxicity grading and management
-
Grade 1
- Start nonsedating, antiseizure medicines (eg, levetiracetam) for seizure prophylaxis
- <72 hr: Consider dexamethasone 10 mg IV q12-24hr for 2-3 days
- ≥72 hr: Observe
-
Grade 2
- Start nonsedating, antiseizure medicines (eg, levetiracetam) for seizure prophylaxis
- Dexamethasone 10 mg IV q12hr for 2-3 days, or longer for persistent symptoms; consider taper for total steroid exposure >3 days
- If no improvement after 24 hr or worsening of neurologic toxicity, increase dexamethasone to up to 20 mg IV q6hr
- If no improvement after another 24 hr, rapidly progressing symptoms, or life-threatening complications arise, give methylprednisolone (2 mg/kg loading dose, followed by 2 mg/kg QID; taper within 7 days)
-
Grade 3
- Start nonsedating, antiseizure medicines (eg, levetiracetam) for seizure prophylaxis
- Dexamethasone 10-20 mg IV q8-12
- Steroids not recommended for isolated Grade 3 headaches
- If no improvement after 24 hr or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2)
- If cerebral edema suspected, consider hyperventilation and hyperosmolar therapy; administer high-dose methylprednisolone 1-2 g IV q24hr prn; taper as clinically indicated and cyclophosphamide 1.5 g/m2
-
Grade 4
- Start nonsedating, antiseizure medicines (eg, levetiracetam) for seizure prophylaxis
- Dexamethasone 20 mg IV q6hr
- If no improvement after 24 hr or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2)
- If cerebral edema suspected, consider hyperventilation and hyperosmolar therapy; give high-dose methylprednisolone and cyclophosphamide (dose and frequency as per Grade 3)
Dosing Considerations
Limitation of use: Not indicated for treatment primary CNS lymphoma
Administer at a certified healthcare facility
Monitor for signs/symptoms of CRS and neurologic toxicities at least daily for 7 days following infusion
Instruct patients to remain within proximity of the certified healthcare facility at least 4 weeks following infusion
Verify pregnancy status of females with reproductive potential
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (187)
- abatacept
abatacept, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- abrocitinib
abrocitinib, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- adalimumab
adalimumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ado-trastuzumab emtansine
ado-trastuzumab emtansine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- alefacept
alefacept, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- alemtuzumab
alemtuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- anakinra
anakinra, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ansuvimab
ansuvimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- antithymocyte globulin equine
antithymocyte globulin equine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- antithymocyte globulin rabbit
antithymocyte globulin rabbit, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- apaziquone
apaziquone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- atoltivimab/maftivimab/odesivimab
atoltivimab/maftivimab/odesivimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- azathioprine
azathioprine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- balstilimab
balstilimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- baricitinib
baricitinib, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- basiliximab
basiliximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- belatacept
belatacept, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- bendamustine
bendamustine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- benralizumab
benralizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- benznidazole
benznidazole, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- betamethasone
betamethasone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- bevacizumab
bevacizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- bezlotoxumab
bezlotoxumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- bimekizumab
bimekizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- botulism immune globulin iv
botulism immune globulin iv, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- brodalumab
brodalumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- busulfan
busulfan, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- C1 esterase inhibitor recombinant
C1 esterase inhibitor recombinant, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- C1 inhibitor human
C1 inhibitor human, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- canakinumab
canakinumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- capecitabine
capecitabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- caplacizumab
caplacizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- carboplatin
carboplatin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- carmustine
carmustine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- certolizumab pegol
certolizumab pegol, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cetuximab
cetuximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- chlorambucil
chlorambucil, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cisplatin
cisplatin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cladribine
cladribine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- clofarabine
clofarabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- corticotropin
corticotropin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- cortisone
cortisone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- cyclophosphamide
cyclophosphamide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cyclosporine
cyclosporine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cytarabine
cytarabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- cytomegalovirus immune globulin (CMV IG)
cytomegalovirus immune globulin (CMV IG), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dacarbazine
dacarbazine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- daclizumab
daclizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- daratumumab
daratumumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- deflazacort
deflazacort, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- denosumab
denosumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dexamethasone
dexamethasone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
lisocabtagene maraleucel, dexamethasone. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity. - dimethyl fumarate
dimethyl fumarate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dinutuximab
dinutuximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- diroximel fumarate
diroximel fumarate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- dupilumab
dupilumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ecallantide
ecallantide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- eculizumab
eculizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- elotuzumab
elotuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- emapalumab
emapalumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- emicizumab
emicizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- etanercept
etanercept, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- filgotinib
filgotinib, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- fingolimod
fingolimod, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- floxuridine
floxuridine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- fludarabine
fludarabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- fludrocortisone
fludrocortisone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- fluorouracil
fluorouracil, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- gemcitabine
gemcitabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- gemtuzumab
gemtuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- glatiramer
glatiramer, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- golimumab
golimumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- guselkumab
guselkumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- hepatitis B immune globulin (HBIG)
hepatitis B immune globulin (HBIG), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- hydrocortisone
hydrocortisone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- hydroxyurea
hydroxyurea, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ibritumomab tiuxetan
ibritumomab tiuxetan, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- icatibant
icatibant, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ifosfamide
ifosfamide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- immune globulin IM (IGIM)
immune globulin IM (IGIM), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- immune globulin IV (IGIV)
immune globulin IV (IGIV), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- immune globulin SC
immune globulin SC, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- inebilizumab
inebilizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- infliximab
infliximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- interferon alfa n3
interferon alfa n3, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- interferon alfacon 1
interferon alfacon 1, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- interferon beta 1a
interferon beta 1a, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- interferon beta 1b
interferon beta 1b, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- iodoquinol
iodoquinol, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ipilimumab
ipilimumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- isotretinoin
isotretinoin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ixekizumab
ixekizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- leflunomide
leflunomide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- lomustine
lomustine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- lurbinectedin
lurbinectedin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mechlorethamine
mechlorethamine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mechlorethamine topical
mechlorethamine topical, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- melphalan
melphalan, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- melphalan flufenamide
melphalan flufenamide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mepolizumab
mepolizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mercaptopurine
mercaptopurine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- methotrexate
methotrexate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- methylprednisolone
methylprednisolone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
lisocabtagene maraleucel, methylprednisolone. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity. - mineral oil topical
mineral oil topical, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mitoxantrone
mitoxantrone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mogamulizumab
mogamulizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mometasone sinus implant
mometasone sinus implant, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- monomethyl fumarate
monomethyl fumarate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- moxetumomab pasudotox
moxetumomab pasudotox, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- muromonab CD3
muromonab CD3, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- mycophenolate
mycophenolate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- narsoplimab
narsoplimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- natalizumab
natalizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
lisocabtagene maraleucel, natalizumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. - nelarabine
nelarabine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- nitazoxanide
nitazoxanide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- nivolumab
nivolumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- obinutuzumab
obinutuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ocrelizumab
ocrelizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ofatumumab
ofatumumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ofatumumab SC
ofatumumab SC, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- olaratumab
olaratumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- omalizumab
omalizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- oportuzumab monatox
oportuzumab monatox, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- oxaliplatin
oxaliplatin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- panitumumab
panitumumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- paromomycin
paromomycin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- peginterferon beta-1a
peginterferon beta-1a, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- pembrolizumab
pembrolizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- pemetrexed
pemetrexed, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- pentostatin
pentostatin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- pimecrolimus
pimecrolimus, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- pralatrexate
pralatrexate, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- prednisolone
prednisolone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- prednisone
prednisone, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- procarbazine
procarbazine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- rabies immune globulin, human (RIG)
rabies immune globulin, human (RIG), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ravulizumab
ravulizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- raxibacumab
raxibacumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- reltecimod
reltecimod, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
lisocabtagene maraleucel, reltecimod. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. - remestemcel-L
remestemcel-L, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- reslizumab
reslizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- Rho(D) immune globulin
Rho(D) immune globulin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- rilonacept
rilonacept, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- risankizumab
risankizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- rituximab
rituximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
lisocabtagene maraleucel, rituximab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. - rituximab-hyaluronidase
rituximab-hyaluronidase, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ruxolitinib topical
ruxolitinib topical, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sarilumab
sarilumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- secukinumab
secukinumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- siltuximab
siltuximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sintilimab
sintilimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sirolimus
sirolimus, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sirolimus intravitreal
sirolimus intravitreal, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sirukumab
sirukumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- spesolimab
spesolimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- streptozocin
streptozocin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- sulfasalazine
sulfasalazine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
lisocabtagene maraleucel, sulfasalazine. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. - sutimlimab
sutimlimab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tacrolimus
tacrolimus, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tacrolimus ointment
tacrolimus ointment, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- temozolomide
temozolomide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- teplizumab
teplizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- teriflunomide
teriflunomide, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tetanus immune globulin (TIG)
tetanus immune globulin (TIG), lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- thioguanine
thioguanine, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- thiotepa
thiotepa, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tinidazole
tinidazole, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tocilizumab
tocilizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tofacitinib
tofacitinib, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tositumomab
tositumomab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- trabectedin
trabectedin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- tralokinumab
tralokinumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- trastuzumab
trastuzumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- trastuzumab deruxtecan
trastuzumab deruxtecan, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- treosulfan
treosulfan, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- triamcinolone acetonide extended-release injectable suspension
triamcinolone acetonide extended-release injectable suspension, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid prophylactic use of systemic corticosteroids as premedication before CAR-T cell therapy. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity.
- ublituximab
ublituximab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- upadacitinib
upadacitinib, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- ustekinumab
ustekinumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- vaccinia immune globulin intravenous
vaccinia immune globulin intravenous, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- varicella zoster immune globulin, human
varicella zoster immune globulin, human, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
- vedolizumab
vedolizumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
lisocabtagene maraleucel, vedolizumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. - voclosporin
voclosporin, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
All grades
- Fatigue (48%)
- Cytokine release syndrome (46%)
- Musculoskeletal pain (37%)
- Nausea (33%)
- Hypogammaglobulinemia (32%)
- Headache (30%)
- Encephalopathy (29%)
- Infections (29%)
- Decreased appetite (28%)
- Diarrhea (26%)
- Hypotension (26%)
- Tachycardia (25%)
- Dizziness (24%)
- Constipation (23%)
- Cough (23%)
- Abdominal pain (21%)
- Vomiting (21%)
- Edema (21%)
- Tremor (16%)
- Fever (16%)
- Dyspnea (16%)
- Insomnia (14%)
- Hypertension (14%)
- Bacterial infections (13%)
- Upper respiratory tract infection (13%)
- Rash (13%)
- Chills (12%)
- Peripheral neuropathy (11%)
- Renal failure (11%)
Grade >3
- Neutropenia (76%)
- Thrombocytopenia (39%)
- Anemia (23%)
- Infections (16%)
- Hypofibrinogenemia (15%)
- Hypophosphatemia (13%)
1-10%
All grades
- Viral infectious disorders (10%)
- Motor dysfunction (10%)
- Aphasia (10%)
- Anxiety (10%)
- Delirium (10%)
- Hemorrhage (10%)
Grade >3
- Encephalopathy (9%)
- Bacterial infections (5%)
- Hypertension (4.5%)
- Cytokine release syndrome (4.1%)
- Fatigue (3.4%)
- Hypotension (3.4%)
- Abdominal pain (3%)
- Renal failure (3%)
- Decreased appetite (2.6%)
- Dizziness (2.6%)
- Dyspnea (2.6%)
- Musculoskeletal pain (2.2%)
- Aphasia (2.2%)
- Delirium (2.2%)
- Nausea (1.5%)
- Hemorrhage (1.5%)
- Viral infections (1.5%)
- Edema (1.1%)
- Motor dysfunction (1.1%)
- Headache (1.1%)
<1%
Grade >3
- Upper respiratory tract infection (0.7%)
- Diarrhea (0.4%)
- Vomiting (0.4%)
- Insomnia (0.4%)
- Rash (0.4%)
Warnings
Black Box Warnings
Cytokine release syndrome
- Cytokine release syndrome (CRS), including fatal or life-threatening reactions, reported in a majority of patients
- Do not administer to patients with active infection or inflammatory disorders
- Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids
- Patients should seek immediate medical attention if signs or symptoms of CRS occur at any time; at the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab, and corticosteroids as indicated
Neurological toxicities
- Neurologic toxicities, including life-threatening reactions, reported; these may occur concurrently with CRS or after CRS resolution; monitor and provide supportive care and/or corticosteroids as needed
- The most common neurological toxicities were encephalopathy, headache, tremor, aphasia, and delirium
- Monitor for neurological events for at least 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities
Restricted access program
- Available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS program
- Further information is available at www.yescartatecartusrems.com or 1-888-423-5436
-
REMS requirements
- Healthcare facilities that dispense and administer lisocabtagene maraleucel must be enrolled and comply with the REMS requirements
- Certified healthcare facilities must have onsite immediate access to tocilizumab and ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hr after CAR T-cell IV infusion, if needed for treatment of CRS
- Certified healthcare facilities must ensure training about CRS management and neurological toxicities for healthcare providers who prescribe, dispense, or administer CAR T-cells
Contraindications
None
Cautions
CRS, including fatal or life-threatening reactions, occurred (see Black Box Warnings and Adverse Effects)
Available only through a restricted access program
Allergic reactions may occur during infusion; serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide in the product
Serious infections, including life-threatening or fatal infections, reported; before administering, infection prophylaxis for neutropenia should follow local guidelines; monitor for signs and symptoms of infection after treatment and manage infections with broad-spectrum antibiotics, fluids, and other supportive care
Viral reactivation can occur; hepatitis B virus (HBV) reactivation can result in fulminant hepatitis, hepatic failure, and death; perform screening for HBV, hepatitis C virus, and HIV in accordance with clinical guidelines before collection of cells for manufacturing
Prolonged cytopenias may occur and last for several weeks following lymphodepleting chemotherapy and CAR T-cell infusion; monitor blood cell counts prior to and after therapy administration
B-cell aplasia and hypogammaglobulinemia can occur; monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement standard guidelines
Secondary malignancies may develop; monitor patient life-long for secondary malignancies
Neurological toxicities
- Neurological toxicities, which may be severe or life-threatening, can occur following treatment
- The most common neurologic toxicities include encephalopathy, tremor, aphasia, delirium, headache, ataxia, and dizziness
- Serious events including cerebral edema and seizures occurred; fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, were reported
- Owing to the potential for neurological events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following treatment; advise patients to refrain from driving and engaging in hazardous occupations or activities
- Monitor daily during first week following infusion for signs and symptoms of neurologic toxicities, then at least weekly for 4 weeks
- HIV and the lentivirus used to make lisocabtagene maraleucel have limited, short spans of identical genetic material (RNA); therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received lisocabtagene maraleucel
Immunization with live viral vaccines
- Safety of immunization with live viral vaccines during or following treatment has not been studied
- Vaccination with live-virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CAR T-cell treatment, and until immune recovery afterwards
Pregnancy & Lactation
Pregnancy
Data are not available in pregnant females
No animal reproductive and developmental toxicity studies have been conducted
Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobulinemia
Not recommended during pregnancy, and pregnancy after infusion should be discussed with treating physician
Verify pregnancy status of females with reproductive potential; sexually active females of reproductive potential should have a pregnancy test prior to starting treatment
Infertility: Data are unavailable
Contraception
- See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy
- Limited exposure data available concerning the duration of contraception following treatment
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
CD19-directed genetically modified autologous T-cell immunotherapy that involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells
Following anti-CD19 CAR T-cell engagement with CD19-expressing target cells, the CD28, 4-1BB (CD137), and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T-cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines
This cascade of events leads to killing of CD19-expressing cells
Absorption
Peak plasma time: 12 days
Peak plasma concentration, median: 35,335 copies/mcg (responsive patients); 15,527 copies/mcg (nonresponsive [NR] patients)
AUC (0-28d): 273,552 copies/mcg⋅day (responsive patients); 155,240 copies/mcg⋅day (NR patients)
Elimination
Present in peripheral blood for up to 2 yr
Administration
IV Preparation
Thawing
- Carefully remove vials from cartons and place on protective barrier pad
- Thaw at room temperature until there is no visible ice in vials
- Thaw all vials at the same time
- Keep CD8 and CD4 components separate
Preparing syringes
- Based on concentration of CAR-positive viable T cells for each component, >1 vial of each of the CD8 and CD4 components may be required to complete a dose
- Prepare separate syringes for each CD8 or CD4 component vial received
- Volume drawn up and infused may differ for each component as indicated on the RFI Certificate; do NOT draw up excess volume into syringe
- Each vial contains 5 mL with a total extractable volume of 4.6 mL of CD8 or CD4 component T cells; RFI Certificate for each component indicates the volume (mL) of cells to be drawn up into each syringe
- Use the smallest Luer-lock tip syringe necessary (1, 3, or 5 mL) to draw up specified volume from each vial
- Use 5-mL syringe for volumes <3 mL
- Draw up CD8 component first; affix CD8 syringe labels to syringe(s) beforehand
- See specific instructions and diagrams in prescribing information for needle gauge, length, and angle when puncturing port septum
- Repeat process for CD4 component
IV Administration
- For autologous use only
- Do NOT use leukodepleting filter
- Ensure tocilizumab and emergency equipment are available before infusion and during the recovery period
- Confirm patient identity matches identifiers on syringe label
- Proceed with administration as soon as possible after preparation
- Total time from removal from frozen storage to patient administration should not exceed 2 hr as indicated by the time entered on the syringe label
Administration steps
- Use IV 0.9% NaCl to flush all infusion tubing before and after each CD8 or CD4 component administration
- Administer entire volume of CD8 component IV at infusion rate of ~0.5 mL/minute, using the closest port or Y-arm
- NOTE: Infusion time will vary, but usually <15 minutes for each component
- If >1 syringe required for full cell dose of CD8 component, administer volume in each syringe consecutively without any time between administering the contents of the syringes (unless there is a clinical reason [eg, infusion reaction] to hold the dose)
- After CD8 component administered, flush tubing with 0.9% NaCl, using enough volume to clear tubing and length of IV catheter
- Administer CD4 component second, immediately after administration of CD8 component completed, using steps described for the CD8 component, then flush tubing as described
- Follow universal precautions and local biosafety guidelines applicable for handling and disposal, to avoid potential transmission of infectious disease
Storage
Shipped directly to cell lab or clinical pharmacy associated with infusion center in vapor phase of a liquid nitrogen shipper
Store vials in the vapor phase of liquid nitrogen (≤ -130ºC) in a temperature-monitored system
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Formulary
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