Version May 2024
The FDA has received reports of T-cell malignancies in patients treated with BCMA-directed or CD19-directed autologous CAR T cell immunotherapies. Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action.
Further information may be found at https://www.fda.gov/safety/medical-product-safety-information/bcma-directed-or-cd19-directed-autologous-chimeric-antigen-receptor-car-t-cell-immunotherapies-fda.
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving lisocabtagene maraleucel. Do not administer lisocabtagene maraleucel to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving lisocabtagene maraleucel, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with lisocabtagene maraleucel. Provide supportive care and/or corticosteroids as needed.
Lisocabtagene maraleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
For autologous use only; confirm patient identity matches cartons, vials, and syringe labels prior to infusion. Do not infuse if information on the patient-specific labels do not match the intended patient. The CD8 and CD4 components are supplied in separate vials; more than 1 vial of each component may be required for a complete dose. Delay the lisocabtagene maraleucel infusion for unresolved serious adverse events from preceding chemotherapies, active uncontrolled infection, clinically significant active systemic infections, active inflammatory disorders, or active graft-vs-host disease.
Note: A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide) for 3 days, followed by lisocabtagene maraleucel 2 to 7 days after completion of lymphodepleting chemotherapy. Confirm availability of autologous lisocabtagene maraleucel prior to initiating lymphodepleting chemotherapy. Ensure tocilizumab (2 doses) and emergency equipment are available prior to lisocabtagene maraleucel infusion and during recovery period.
Premedication: Premedicate with acetaminophen 650 mg orally and diphenhydramine 25 to 50 mg IV or orally (or another H1 antihistamine) 30 to 60 minutes prior to lisocabtagene maraleucel infusion to minimize the risk of infusion reaction. Avoid prophylactic systemic corticosteroids as they may interfere with the lisocabtagene maraleucel activity.
Prophylaxis: Administer prophylactic antimicrobials prior to lisocabtagene maraleucel according to standard institutional guidelines. In patients with a prior history of hepatitis B virus (HBV), consider concurrent antiviral suppressive therapy to prevent HBV reactivation according to standard institutional guidelines.
Large B-cell lymphoma, relapsed or refractory: Note: Actual cell counts and volumes for infusion are on the release for infusion (RFI) certificates.
After 1 line of systemic therapy: IV: 90 to 110 × 106 CAR-positive viable T-cells (consisting of 1:1 CD8 and CD4 components).
After 2 or more lines of systemic therapy: IV: 50 to 110 × 106 CAR-positive viable T-cells (consisting of 1:1 CD8 and CD4 components).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Cytokine release syndrome: Monitor for cytokine release syndrome (CRS); if fever, hypoxia, and hypotension occur, evaluate for other causes and manage as appropriate. If CRS is suspected, manage according to the table below. Initiate supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated at first sign of CRS. Monitor patients with ≥ grade 2 CRS (eg, hypotension unresponsive to fluids or hypoxia requiring supplemental oxygen) with continuous cardiac telemetry and pulse oximetry. Consider obtaining echocardiogram to assess cardiac function in patients with severe CRS. Severe or life-threatening CRS may require intensive care supportive therapy. If concurrent neurologic toxicity is suspected during CRS, administer more aggressive corticosteroid intervention (based on the CRS and Neurotoxicity tables), tocilizumab (according to CRS table), and antiseizure mediations (according to Neurotoxicity table).
|
CRS grade |
Tocilizumab |
Corticosteroidsa |
|---|---|---|
|
aIf corticosteroids are initiated, continue corticosteroids for at least 3 doses or until complete symptom resolution, and consider corticosteroid taper. | ||
|
Grade 1: Fever |
If <72 hours after infusion, consider tocilizumab 8 mg/kg (maximum dose: 800 mg) IV over 1 hour. If ≥72 hours, manage symptomatically. |
If <72 hours after infusion, consider dexamethasone 10 mg IV every 24 hours. If ≥72 hours, manage 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 (maximum dose: 800 mg) IV over 1 hour, repeat every 8 hours as needed if not responsive to IV fluids or increasing supplemental oxygen. Maximum of 3 tocilizumab doses/24 hours, and maximum total of 4 tocilizumab doses. |
If <72 hours after infusion, administer dexamethasone 10 mg IV every 12 to 24 hours. If ≥72 hours after infusion, consider dexamethasone 10 mg IV every 12 to 24 hours. |
|
If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dexamethasone to 10 to 20 mg IV every 6 to 12 hours. If no improvement or continued rapid progression, maximize dexamethasone, or switch to methylprednisolone 2 mg/kg IV if needed. After 2 tocilizumab doses, consider alternative immunosuppression. Do not exceed 3 tocilizumab doses/24 hours, and maximum total of 4 tocilizumab doses. | ||
|
Grade 3: Symptoms require and respond to aggressive intervention. Oxygen requirement ≥40% FiO2, or hypotension requiring high-dose or multiple vasopressors, or grade 3 organ toxicity, or grade 4 transaminitis. |
Manage per grade 2. |
Administer dexamethasone 10 mg IV every 12 hours. |
|
If no improvement within 24 hours or rapid CRS progression, repeat tocilizumab and escalate dexamethasone to 10 to 20 mg IV every 6 to 12 hours. If no improvement or continued rapid progression, maximize dexamethasone, or switch to methylprednisolone 2 mg/kg IV if needed. After 2 tocilizumab doses, consider alternative immunosuppression. Do not exceed 3 tocilizumab doses/24 hours, and maximum total of 4 tocilizumab doses. | ||
|
Grade 4: Life-threatening symptoms. Ventilator support required or CVVHD required or grade 4 organ toxicity (excluding transaminitis). |
Manage per grade 2. |
Administer dexamethasone 20 mg IV every 6 hours. |
|
If no improvement within 24 hours or rapid CRS progression, escalate tocilizumab and corticosteroid use. If no improvement or continued rapid progression, maximize dexamethasone, or switch to methylprednisolone 2 mg/kg IV if needed. After 2 tocilizumab doses, consider alternative immunosuppression. Do not exceed 3 tocilizumab doses/24 hours, and maximum total of 4 tocilizumab doses. | ||
Neurotoxicity: Monitor for signs/symptoms of neurologic toxicities and rule out other causes of neurologic symptoms. Provide intensive care supportive therapy for severe or life-threatening neurologic toxicities. If neurotoxicity is suspected, manage according to the Neurotoxicity table. If concurrent CRS is suspected during neurotoxicity, administer more aggressive corticosteroid intervention (based on the CRS and Neurotoxicity tables), tocilizumab (according to CRS table), and antiseizure mediations (according to Neurotoxicity table).
|
Neurotoxicity grade |
Corticosteroids and antiseizure medication |
|---|---|
|
Grade 1 |
Initiate seizure prophylaxis with nonsedating antiseizure medications (eg, levetiracetam). If ≥72 hours after infusion, observe. If <72 hours after infusion, consider dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days. |
|
Grade 2 |
Initiate seizure prophylaxis with nonsedating antiseizure medications (eg, levetiracetam). Administer dexamethasone 10 mg IV every 12 hours for 2 to 3 days (or longer for persistent symptoms). Consider taper for a total corticosteroid exposure of >3 days. If no improvement after 24 hours, or worsening neurologic toxicity, increase dexamethasone dose and/or frequency up to a maximum of 20 mg IV every 6 hours. If no improvement after another 24 hours, rapidly progressing symptoms, or for life-threatening complications, administer methylprednisolone (2 mg/kg IV loading dose, followed by 0.5 mg/kg IV every 6 hours; taper within 7 days). |
|
Grade 3 |
Initiate seizure prophylaxis with nonsedating antiseizure medications (eg, levetiracetam). Administer dexamethasone 10 to 20 mg IV every 8 to 12 hours (corticosteroids are not recommended for isolated grade 3 headache). If no improvement after 24 hours, or worsening neurologic toxicity, escalate to methylprednisolone (2 mg/kg IV loading dose, followed by 0.5 mg/kg IV every 6 hours; taper within 7 days). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Administer methylprednisolone 1 to 2 g IV, repeat every 24 hours if needed and taper as clinically indicated. Administer cyclophosphamide 1.5 g/m2 IV. |
|
Grade 4 |
Initiate seizure prophylaxis with nonsedating antiseizure medications (eg, levetiracetam). Administer dexamethasone 20 mg IV every 6 hours. If no improvement after 24 hours, or worsening neurologic toxicity, escalate to methylprednisolone (2 mg/kg IV loading dose, followed by 0.5 mg/kg IV every 6 hours; taper within 7 days). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Administer methylprednisolone 1 to 2 g IV, repeat every 24 hours if needed and taper as clinically indicated. Administer cyclophosphamide 1.5 g/m2 IV. |
Other toxicities:
Hypogammaglobulinemia: Manage with infection precautions, antibiotic prophylaxis, and immune globulin replacement as clinically indicated.
Infection: Administer prophylactic antimicrobials prior to lisocabtagene maraleucel according to standard institutional guidelines.
Neutropenic fever: Evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as clinically indicated.
Refer to adult dosing.
Adverse reactions reported in adults.
>10%:
Cardiovascular: Edema (13% to 21%), hypertension (7% to 14%), hypotension (15% to 26%), tachycardia (10% to 25%)
Dermatologic: Skin rash (7% to 13%)
Endocrine & metabolic: Decreased serum phosphate (grade 3/4: 16%)
Gastrointestinal: Abdominal pain (7% to 21%), constipation (11% to 23%), decreased appetite (13% to 28%), diarrhea (15% to 26%; grades ≥3: <1%), nausea (24% to 33%; grades ≥3: 2%), vomiting (8% to 21%; grades ≥3: <1%)
Hematologic & oncologic: Decreased hemoglobin (grade 3/4: 30% to 32%), decreased neutrophils (grade 3/4: 57% to 89%), decreased platelet count (grade 3/4: 20% to 48%), decreased serum fibrinogen (grade 3/4: 14%), hemorrhage (10% to 12%; grades ≥3: 2%; including conjunctival hemorrhage, epistaxis, intracranial hemorrhage, pulmonary hemorrhage, retinal hemorrhage, vaginal hemorrhage), hypogammaglobulinemia (11% to 28%), lymphocytopenia (grade 3/4: 64% to 98%)
Hypersensitivity: Cytokine release syndrome (39% to 49%)
Immunologic: Antibody development (1% to 11%)
Infection: Bacterial infection (10% to 13%), infection (12% to 29%; including serious infection)
Nervous system: Chills (12%), dizziness (16% to 24%), encephalopathy (8% to 29%), fatigue (28% to 48%), headache (11% to 34%), insomnia (11% to 15%), motor dysfunction (7% to 12%; including blepharoptosis, muscle rigidity, muscle spasticity, myasthenia, myoclonus, myopathy), neurological signs and symptoms (27% to 35%; including brain edema [<1%], leukoencephalopathy, immune effector cell-associated neurotoxicity syndrome, seizure [1%]), peripheral neuropathy (5% to 11%), tremor (11% to 16%)
Neuromuscular & skeletal: Musculoskeletal pain (23% to 37%)
Renal: Renal failure syndrome (3% to 11%)
Respiratory: Cough (11% to 23%), dyspnea (8% to 16%), upper respiratory tract infection (13%)
Miscellaneous: Fever (16% to 55%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (6%), cardiomyopathy (2%), thrombosis (7% to 8%)
Gastrointestinal: Gastrointestinal hemorrhage (4% to 5%)
Genitourinary: Urinary tract infection (4%)
Hematologic & oncologic: Febrile neutropenia (2% to 10%; grades ≥3: 10%), hemophagocytic lymphohistiocytosis (1%)
Hypersensitivity: Infusion-related reaction (2%)
Infection: Fungal infection (5% to 8%), sepsis (3% to 10%), viral infection (3% to 10%)
Nervous system: Abnormal gait (≤7%), anxiety (10%), aphasia (5% to 10%), ataxia (≤7%), cerebrovascular disease (2%), delirium (2% to 10%), paresis (1% to 3%)
Ophthalmic: Blurred vision (3%), visual disturbance (5%)
Respiratory: Hypoxia (5% to 6%), pleural effusion (7%), pneumonia (2% to 8%)
<1%:
Hematologic & oncologic: Tumor lysis syndrome
Frequency not defined:
Cardiovascular: Pulmonary embolism
Nervous system: Confusion
Postmarketing: Hematologic & oncologic: Hematologic malignancy (T-cell) (FDA Safety Communication 2023)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to lisocabtagene maraleucel or any component of the formulation.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS) has commonly occurred with lisocabtagene maraleucel; grade 3, life-threatening, and fatal CRS have occurred. The median time to onset of CRS in patients receiving lisocabtagene maraleucel after ≥2 lines of systemic therapy was 5 days (range: 1 to 15 days); the median time to onset of CRS in patients receiving lisocabtagene maraleucel after 1 line of systemic therapy was 4 days (range: 1 to 63 days). CRS resolved in most patients, with a median CRS duration of 4 to 5 days (range: 1 to 17 days). The most common CRS manifestations included fever, chills, hypotension, tachycardia, headache, and hypoxia. Serious events associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and/or hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Two doses of tocilizumab must be available prior to lisocabtagene maraleucel infusion. Patients should seek immediate medical attention if signs/symptoms of CRS occur at any time.
• Cytopenias: Prolonged cytopenias may occur for several weeks after lymphodepleting chemotherapy and lisocabtagene maraleucel. Grade 3 or higher cytopenias persisting at day 29 after lisocabtagene maraleucel included thrombocytopenia, neutropenia, and anemia.
• Hepatitis B virus reactivation: Hepatitis B virus reactivation (sometimes resulting in fulminant hepatitis, hepatic failure, and death) can occur in patients treated with medication directed against B cells.
• Hypersensitivity: Allergic reactions may occur with lisocabtagene maraleucel.
• Hypogammaglobulinemia: Hypogammaglobulinemia and B-cell aplasia may occur in patients receiving lisocabtagene maraleucel.
• Infections: Infections occurred commonly with lisocabtagene maraleucel; grade 3 or higher, life-threatening, or fatal infections have occurred. Infections included bacterial, viral, and fungal infections, as well as infection with unspecified pathogens. Neutropenic fever has been observed and may be concurrent with CRS.
• Neurotoxicity: Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome (ICANS) have occurred with lisocabtagene maraleucel, including grade 3, life-threatening, and fatal reactions. Neurotoxicity may occur concurrently with CRS, after CRS resolution, or in the absence of CRS. Neurotoxicity may overlap with CRS, with the onset of neurologic toxicity either after, before, or on the same day as CRS. The median time to onset of the first neurologic event in all patients combined receiving lisocabtagene maraleucel for large B-cell lymphoma was 8 days (range: 1 to 63 days), with the majority of events occurring by 16 days following lisocabtagene maraleucel infusion. Neurotoxicity resolved in most patients, with a median duration of 11 days (range: 1 to 119 days). The most common neurotoxicities included encephalopathy, tremor, aphasia, delirium, headache, and dizziness; serious or fatal events including cerebral edema, seizures, and/or leukoencephalopathy (although some cases were attributed to lymphodepleting therapy). Some serious events may also be attributable to lymphodepleting chemotherapy. Patients should seek immediate medical attention for signs/symptoms of neurologic toxicity. Due to the potential for neurologic events, including altered mental status or seizures, patients receiving lisocabtagene maraleucel are at risk for altered or decreased consciousness or coordination in the 8 weeks following administration; advise patients to refrain for at least 8 weeks from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery.
• Secondary malignancies: Patients treated with lisocabtagene maraleucel may develop secondary malignancies. If a secondary malignancy develops, contact the manufacturer (1-888-805-4555) for reporting and to obtain patient sampling instructions for testing.
Concurrent drug therapy issues:
• Immunizations: Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during lisocabtagene maraleucel treatment, and until immune recovery following treatment with lisocabtagene maraleucel. Immunization with live viral vaccines during or following lisocabtagene maraleucel has not been studied.
Dosage form specific issues:
• Dimethyl sulfoxide: Lisocabtagene maraleucel contains dimethyl sulfoxide (DMSO), which has been associated with serious hypersensitivity reactions (including anaphylaxis).
Other warnings/precautions:
• REMS program: Lisocabtagene maraleucel is available only through a restricted program under a REMS called the BREYANZI REMS. Information is available at https://www.BreyanziREMS.com or at 1-888-423-5436.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Breyanzi: 70 million cells (1 ea) [contains albumin human]
No
Suspension (Breyanzi Intravenous)
70000000CELLS/ML (per each): $0.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Breyanzi: 70 million cells (1 ea) [contains albumin human]
IV: For IV use only. Administer in a health care facility. Coordinate the timing of administration with thawing. Administer as soon as possible after syringe preparation (must be administered within 2 hours of initiation of thawing). Do not use a leukodepleting filter.
Flush infusion tubing with NS prior to and after each CD8 or CD4 component. Using the Y-site or port closest to the patient, administer the entire volume of the CD8 component syringe(s) at a rate of ~0.5 mL/minute; if the CD8 component requires more than 1 syringe, administer the volume in each syringe consecutively without delay in between (unless there is a clinical reason to hold the balance of the dose, such as infusion reaction). Administration time will vary, but is usually <15 minutes for each component. After the CD8 component has been administered, flush the line with NS, using enough NS volume to clear the tubing and the length of the catheter. Administer the CD4 component immediately after the flush (follow the same process as used for the CD8 component), then flush with NS after the CD4 component had been administered.
Prior to administration: Ensure tocilizumab and emergency equipment are available prior to infusion and during recovery period. Confirm patient identity and match to patient identifiers on the syringe labels. Apply universal precautions for product handling. Premedicate with acetaminophen 650 mg orally and diphenhydramine 25 to 50 mg IV or orally (or other H1 antihistamine) 30 to 60 minutes prior to lisocabtagene maraleucel administration. Avoid prophylactic systemic corticosteroids, as they may interfere with lisocabtagene maraleucel activity.
Monitor patient daily at the health care facility for at least 7 days after cell infusion; patient should remain within proximity of the facility for at least 4 weeks after infusion.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Breyanzi: https://packageinserts.bms.com/medguide/medguide_breyanzi.pdf
Large B-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (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 in adults who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation due to comorbidities or age; or relapsed or refractory disease after 2 or more lines of systemic therapy.
Limitations of use: Not indicated for the treatment of primary CNS lymphoma.
Lisocabtagene maraleucel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, elivaldogene autotemcel, idecabtagene vicleucel, sipuleucel-T, tisagenlecleucel.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy. Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary mRNA vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who could become pregnant.
The need for and duration of contraception following exposure to lisocabtagene maraleucel is not known. In a clinical trial, females who could become pregnant were required to use highly effective contraception for 1 year after the last dose of lisocabtagene maraleucel; males with female partners who could become pregnant were required to use barrier contraception for 1 year after the last dose (Abramson 2020). Refer to the fludarabine and cyclophosphamide monographs for information concerning the need for effective contraception associated with lymphodepleting chemotherapy.
Animal reproduction studies have not been conducted. Based on the mechanism of action, B-cell lymphocytopenia and hypogammaglobulinemia may occur if fetal exposure to lisocabtagene maraleucel occurs. Pregnant patients were excluded from a clinical trial (Abramson 2020).
It is not known if lisocabtagene maraleucel is present in breast milk.
According to the manufacturer, the decision to breastfeed should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Patients who were breastfeeding were excluded from a clinical trial (Abramson 2020).
Screen for hepatitis B virus (HBV), hepatitis C virus, and HIV in accordance with clinical guidelines prior to collection of cells for manufacturing. Monitor CBC prior to and after lisocabtagene maraleucel administration. Evaluate pregnancy status prior to use (in patients who could become pregnant). Monitor immunoglobulin levels after lisocabtagene maraleucel treatment.
Monitor for cytokine release syndrome (CRS) and signs/symptoms of neurotoxicity during therapy and for at least 4 weeks after infusion. For ≥ grade 2 CRS, perform continuous cardiac telemetry and pulse oximetry; consider obtaining echocardiogram to assess cardiac function in patients with severe CRS. Monitor patient daily at the health care facility for at least 7 days after cell infusion. Monitor for signs/symptoms of infection before and after lisocabtagene maraleucel administration. Monitor (lifelong) for secondary malignancies.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins; a baseline echocardiography is recommended in patients with preexisting cardiovascular disease; consider baseline echocardiography in all patients; for patients who develop ≥ grade 2 cytokine release syndrome, assess natriuretic peptides and troponins, and obtain echocardiography (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
Lisocabtagene maraleucel is a CD19-directed genetically modified autologous T-cell immunotherapy in which a patient's T-cells are reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing cells (malignant and normal). Lisocabtagene maraleucel has a defined composition of CD8-and CD4-positive CAR T-cells. CAR is comprised of an FMC63 monoclonal antibody-derived single chain variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3 zeta activation domain. CD3 zeta signaling initiates activation and antitumor activity, while 4-1BB (CD137) signaling enhances T-cell expansion. CAR binding to CD19 (expressed on cell surfaces) induces activation and proliferation of CAR T-cells, release of pro-inflammatory cytokines, and results in cytotoxic destruction of target cells. Lisocabtagene maraleucel is prepared from the patient's T-cells, which are obtained via leukapheresis.
Note: Lisocabtagene maraleucel exhibits an initial rapid expansion followed by a bi-exponential decline; lisocabtagene maraleucel was present in peripheral blood for an estimated median of ~12 months (range: up to ~2 years). In patients who received tocilizumab and/or corticosteroids to manage cytokine release syndrome (CRS) and/or neurologic toxicity, the lisocabtagene maraleucel AUC0 to 28d and Cmax are higher compared to patients who did not receive tocilizumab or corticosteroids.
Onset: Median time to first response (complete or partial response): 1 month (range: 0.7 to 8.9 months).
Time to peak: Median time to CAR T-cell peak expansion: 12 days (Abramson 2020).
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