2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

For subcutaneous injection only.

The recommended dosing schedule for TECVAYLI is provided in Table 1. The recommended dosage of TECVAYLI is step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity. In patients who have achieved and maintained a complete response or better for a minimum of 6 months, the dosing frequency may be decreased to 1.5 mg/kg every two weeks until disease progression or unacceptable toxicity.

Administer pretreatment medications prior to each dose of the TECVAYLI step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described in Table 1 [see Dosage and Administration (2.2)] .

Administer TECVAYLI subcutaneously according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome (CRS). Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.4)and Warnings and Precautions (5.1, 5.2)] .

Table 1: TECVAYLI Dosing Schedule
Dosing schedule	Day	Dose
* See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. † Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions. ‡ First treatment dose may be given between 2 to 4 days after step-up dose 2 and may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions.
All Patients
Step-up dosing schedule *	Day 1	Step-up dose 1	0.06 mg/kg
	Day 4 †	Step-up dose 2	0.3 mg/kg
	Day 7 ‡	First treatment dose	1.5 mg/kg
Weekly dosing schedule *	One week after first treatment dose and weekly thereafter	Subsequent treatment doses	1.5 mg/kg once weekly
Patients who have achieved and maintained a complete response or better for a minimum of 6 months
Biweekly (every two weeks) dosing schedule *	The dosing frequency may be decreased to 1.5 mg/kg every two weeks.

Refer to Tables 7, 8, and 9 to determine the dosage based on predetermined weight ranges [see Dosage and Administration (2.5)] .

2.2 Recommended Pretreatment Medications

Administer the following pretreatment medications 1 to 3 hours before each dose of the TECVAYLI step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose (see Table 1), to reduce the risk of CRS [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)] .

Corticosteroid (oral or intravenous dexamethasone 16 mg)
Histamine-1 (H1) receptor antagonist (oral or intravenous diphenhydramine 50 mg or equivalent)
Antipyretics (oral or intravenous acetaminophen 650 mg to 1,000 mg or equivalent)

Administration of pretreatment medications may be required prior to administration of subsequent doses of TECVAYLI in the following patients:

Patients who repeat doses within the TECVAYLI step-up dosing schedule following a dose delay [see Dosage and Administration (2.3)].
Patients who experienced CRS following the prior dose of TECVAYLI [see Dosage and Administration (2.4)].

Prophylaxis for Herpes Zoster Reactivation

Prior to starting treatment with TECVAYLI, consider initiation of antiviral prophylaxis to prevent herpes zoster reactivation per guidelines.

2.3 Restarting TECVAYLI after Dosage Delay

If a dose of TECVAYLI is delayed, restart therapy based on the recommendations in Table 2 and resume the treatment schedule accordingly [see Dosage and Administration (2.1)] . Administer pretreatment medications as indicated in Table 2 .Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.4) and Warnings and Precautions (5.1, 5.2)].

Table 2: Recommendations for Restarting Therapy with TECVAYLI After Dose Delay
Last dose administered	Time since the last dose administered	Action
* Administer pretreatment medications prior to TECVAYLI dose and monitor patients accordingly [see Dosage and Administration (2.2, 2.5)]. † Consider benefit-risk of restarting TECVAYLI in patients who require a dose delay of more than 28 days due to an adverse reaction.
Step-up dose 1	More than 7 days	Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). *
Step-up dose 2	8 days to 28 days	Repeat step-up dose 2 (0.3 mg/kg) *and continue TECVAYLI step-up dosing schedule.
Step-up dose 2	More than 28 days †	Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). *
Any weekly treatment dose	28 days or less	Continue TECVAYLI at last treatment dose in weekly schedule (1.5 mg/kg once weekly; see Table 1).
	29 days to 56 days †	Restart TECVAYLI step-up dosing schedule at step-up dose 2 (0.3 mg/kg). *
	More than 56 days †	Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). *
Any biweekly (every two weeks) treatment dose	63 days or less †	Continue TECVAYLI at last treatment dose in biweekly schedule (1.5 mg/kg every two weeks; see Table 1).
	64 days to 112 days †	Restart TECVAYLI step-up dosing schedule at step up dose 2 (0.3 mg/kg). *
	More than 112 days †	Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). *

2.4 Dosage Modifications for Adverse Reactions

Dosage reductions of TECVAYLI are not recommended.

Dosage delays may be required to manage toxicities related to TECVAYLI [see Warnings and Precautions (5)].

See Tables 3, 4, and 5 for recommended actions for adverse reactions of CRS, neurologic toxicity, and ICANS. See Table 6 for recommended actions for other adverse reactions following administration of TECVAYLI.

Management of CRS, Neurologic Toxicity and ICANS

Cytokine Release Syndrome (CRS)

Management recommendations for CRS are summarized in Table 3.

Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate and treat other causes of fever, hypoxia, and hypotension.

If CRS is suspected, withhold TECVAYLI until CRS resolves. Manage according to the recommendations in Table 3 and consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.

Table 3: Recommendations for Management of Cytokine Release Syndrome
Grade *	Presenting Symptoms	Actions
* Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS. † Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy. ‡ See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. § Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.
Grade 1	Temperature ≥100.4°F (38°C) †	Withhold TECVAYLI until CRS resolves. Administer pretreatment medications prior to next dose of TECVAYLI. ‡
Grade 2	Temperature ≥100.4°F (38°C) †with: Hypotension responsive to fluids and not requiring vasopressors, and/or, Oxygen requirement of low-flow nasal cannula §or blow-by.	Withhold TECVAYLI until CRS resolves. Administer pretreatment medications prior to next dose of TECVAYLI. ‡ Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1)]. ‡
Grade 3	Temperature ≥100.4°F (38°C) †with: Hypotension requiring one vasopressor with or without vasopressin, and/or, Oxygen requirement of high-flow nasal cannula §, facemask, non-rebreather mask, or Venturi mask.	First Occurrence of Grade 3 CRS with Duration Less than 48 Hours: Withhold TECVAYLI until CRS resolves. Provide supportive therapy, which may include intensive care. Administer pretreatment medications prior to next dose of TECVAYLI. ‡ Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1)]. ‡
Grade 3		Recurrent Grade 3 CRS or Grade 3 CRS with Duration 48 Hours or Longer: Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care.
Grade 4	Temperature ≥100.4°F (38°C) †with: Hypotension requiring multiple vasopressors (excluding vasopressin), and/or, Oxygen requirement of positive pressure (e.g., continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation, and mechanical ventilation).	Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care.

Neurologic Toxicity and ICANS

Management recommendations for neurologic toxicity and ICANS are summarized in Tables 4 and 5.

At the first sign of neurologic toxicity, including ICANS, withhold TECVAYLI and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS [see Warnings and Precautions (5.2)] . Manage ICANS according to the recommendations in Table 5 and consider further management per current practice guidelines.

Table 4: Recommendations for Management of Neurologic Toxicity (excluding ICANS)
Adverse Reaction	Severity *	Actions
* Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. † See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)].
Neurologic Toxicity *(excluding ICANS)	Grade 1	Withhold TECVAYLI until neurologic toxicity symptoms resolve or stabilize. †
	Grade 2 Grade 3 (First occurrence)	Withhold TECVAYLI until neurologic toxicity symptoms improve to Grade 1 or less. † Provide supportive therapy.
	Grade 3 (Recurrent) Grade 4	Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care.

Table 5: Recommendations for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome
Grade *	Presenting Symptoms †	Actions
* Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. † Management is determined by the most severe event, not attributable to any other cause. ‡ If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue" = 1 point); Writing (ability to write a standard sentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points. § Not attributable to any other cause. ¶ See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. # All references to dexamethasone administration are dexamethasone or equivalent.
Grade 1	ICE score 7–9 ‡, or depressed level of consciousness §: awakens spontaneously.	Withhold TECVAYLI until ICANS resolves. ¶ Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
Grade 2	ICE score 3–6 ‡, or depressed level of consciousness §: awakens to voice.	Withhold TECVAYLI until ICANS resolves. Administer dexamethasone #10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1)] . ¶
Grade 3	ICE score 0–2 ‡, or depressed level of consciousness §: awakens only to tactile stimulus, or seizures §, either: any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging §.	First Occurrence of Grade 3 ICANS: Withhold TECVAYLI until ICANS resolves. Administer dexamethasone #10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1)] . ¶
Grade 3		Recurrent Grade 3 ICANS: Permanently discontinue TECVAYLI Administer dexamethasone #10 mg intravenously and repeat dose every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.
Grade 4	ICE score 0 ‡, or depressed level of consciousness §: either: patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, or seizures §, either: life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between, or motor findings §: deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral edema §, with signs/symptoms such as: diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing's triad.	Permanently discontinue TECVAYLI. Administer dexamethasone #10 mg intravenously and repeat dose every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Alternatively, consider administration of methylprednisolone 1,000 mg per day intravenously and continue methylprednisolone 1,000 mg per day intravenously for 2 or more days. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.

Table 6: Recommended Dosage Modifications for Other Adverse Reactions
Adverse Reactions	Severity	Actions
* Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. † See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)].
Infections *[see Warnings and Precautions (5.5)]	All Grades	Withhold TECVAYLI in patients with active infection during the step-up dosing schedule. †
	Grade 3	Withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until infection improves to Grade 1 or less. †
	Grade 4	Consider permanent discontinuation of TECVAYLI. If TECVAYLI is not permanently discontinued, withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until infection improves to Grade 1 or less. †
Hematologic Toxicities [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]	Absolute neutrophil count less than 0.5 × 10 9/L	Withhold TECVAYLI until absolute neutrophil count is 0.5 × 10 9/L or higher. †
	Febrile neutropenia	Withhold TECVAYLI until absolute neutrophil count is 1 × 10 9/L or higher and fever resolves. †
	Hemoglobin less than 8 g/dL	Withhold TECVAYLI until hemoglobin is 8 g/dL or higher. †
	Platelet count less than 25,000/mcL Platelet count between 25,000/mcL and 50,000/mcL with bleeding	Withhold TECVAYLI until platelet count is 25,000/mcL or higher and no evidence of bleeding. †
Other Non-Hematologic Adverse Reactions * [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)]	Grade 3	Withhold TECVAYLI until adverse reaction improves to Grade 1 or less. †
	Grade 4	Consider permanent discontinuation of TECVAYLI. If TECVAYLI is not permanently discontinued, withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until adverse reaction improves to Grade 1 or less. †

2.5 Preparation and Administration

TECVAYLI is intended for subcutaneous use by a healthcare provider only.

TECVAYLI should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and ICANS [see Warnings and Precautions (5.1, 5.2)] .

TECVAYLI is a clear to slightly opalescent, colorless to light yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is discolored, or cloudy, or if foreign particles are present.

TECVAYLI 30 mg/3 mL (10 mg/mL) vial and TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration.

Do not combine TECVAYLI vials of different concentrations to achieve treatment dose.

Use aseptic technique to prepare and administer TECVAYLI.

Preparation of TECVAYLI

Refer to the following reference tables for the preparation of TECVAYLI.

Refer to Tables 7, 8, and 9 below to determine the dosage based on predetermined weight ranges.

Use Table 7 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 1 using TECVAYLI 30 mg/3 mL (10 mg/mL) vial.

Table 7: Step-up Dose 1 (0.06 mg/kg) Injection Volumes using TECVAYLI 30 mg/3 mL (10 mg/mL) Vial
Patient Body Weight (kg)	Total Dose (mg)	Volume of Injection (mL)	Number of Vials (1 vial=3 mL)
35 to 39	2.2	0.22	1
40 to 44	2.5	0.25	1
45 to 49	2.8	0.28	1
50 to 59	3.3	0.33	1
60 to 69	3.9	0.39	1
70 to 79	4.5	0.45	1
80 to 89	5.1	0.51	1
90 to 99	5.7	0.57	1
100 to 109	6.3	0.63	1
110 to 119	6.9	0.69	1
120 to 129	7.5	0.75	1
130 to 139	8.1	0.81	1
140 to 149	8.7	0.87	1
150 to 160	9.3	0.93	1

Use Table 8 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 2 using TECVAYLI 30 mg/3 mL (10 mg/mL) vial.

Table 8: Step-up Dose 2 (0.3 mg/kg) Injection Volumes using TECVAYLI 30 mg/3 mL (10 mg/mL) Vial
Patient Body Weight (kg)	Total Dose (mg)	Volume of Injection (mL)	Number of Vials (1 vial=3 mL)
35 to 39	11	1.1	1
40 to 44	13	1.3	1
45 to 49	14	1.4	1
50 to 59	16	1.6	1
60 to 69	19	1.9	1
70 to 79	22	2.2	1
80 to 89	25	2.5	1
90 to 99	28	2.8	1
100 to 109	31	3.1	2
110 to 119	34	3.4	2
120 to 129	37	3.7	2
130 to 139	40	4	2
140 to 149	43	4.3	2
150 to 160	47	4.7	2

Use Table 9 to determine total dose, injection volume and number of vials required based on patient's actual body weight for the treatment dose using TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial.

Table 9: Treatment Dose (1.5 mg/kg) Injection Volumes using TECVAYLI 153 mg/1.7 mL (90 mg/mL) Vial
Patient Body Weight (kg)	Total Dose (mg)	Volume of Injection (mL)	Number of Vials (1 vial=1.7 mL)
35 to 39	56	0.62	1
40 to 44	63	0.7	1
45 to 49	70	0.78	1
50 to 59	82	0.91	1
60 to 69	99	1.1	1
70 to 79	108	1.2	1
80 to 89	126	1.4	1
90 to 99	144	1.6	1
100 to 109	153	1.7	1
110 to 119	171	1.9	2
120 to 129	189	2.1	2
130 to 139	198	2.2	2
140 to 149	216	2.4	2
150 to 160	234	2.6	2

Remove the appropriate strength TECVAYLI vial from refrigerated storage [2°C to 8°C (36°F to 46°F)].

Once removed from refrigerated storage, equilibrate TECVAYLI to ambient temperature [15°C to 30°C (59°F to 86°F)] for at least 15 minutes. Do not warm TECVAYLI in any other way.

Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake.

Withdraw the required injection volume of TECVAYLI from the vial(s) into an appropriately sized syringe using a transfer needle.

Each injection volume should not exceed 2 mL. Divide doses requiring greater than 2 mL equally into multiple syringes.

TECVAYLI is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material.

Replace the transfer needle with an appropriately sized needle for injection.

Administration of TECVAYLI

Inject the required volume of TECVAYLI into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, TECVAYLI may be injected into the subcutaneous tissue at other sites (e.g., thigh). If multiple injections are required, TECVAYLI injections should be at least 2 cm apart.

Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.

Any unused product or waste material should be disposed in accordance with local requirements.

Storage

If the prepared dosing syringe(s) of TECVAYLI is not used immediately, store syringe(s) at 2°C to 8°C (36°F to 46°F) or at ambient temperature 15°C to 30°C (59°F to 86°F) for a maximum of 20 hours. Discard syringe(s) after 20 hours, if not used.

Monitoring

Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.1) and Warnings and Precautions (5.1, 5.2)] .