TECVAYLI

2 DOSAGE AND ADMINISTRATION For subcutaneous injection only. ( 2.1 ) Patients should be hospitalized for 48 hours after administration of both step-up dose 1 and step-up dose 2. Instruct patients to remain within proximity of a healthcare facility and monitored daily for 48 hours after the first treatment dose within the TECVAYLI step-up dosing schedule. ( 2.1 ) See Full Prescribing Information for the recommended dosage for TECVAYLI monotherapy and combination therapy. ( 2.2 , 2.3 ) Administer pretreatment medications as recommended. ( 2.3 ) Refer to Tables 8, 9, 10, and 11 to determine the total dose, injection volume, and number of vials based on the patient's body weight. ( 2.6 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) 2.1 Important Dosage and Administration Information TECVAYLI is for subcutaneous injection only. 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 Tables 1 and 2 [see Dosage and Administration (2.3) ] . Administer TECVAYLI subcutaneously according to the step-up dosing schedule in Tables 1 and 2 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 both step-up dose 1 and step-up dose 2. Instruct patients to remain within proximity of a healthcare facility and monitor them daily for 48 hours after the first treatment dose within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.5) and Warnings and Precautions (5.1 , 5.2) ] . Refer to Tables 8, 9, 10, and 11 to determine the dosage based on predetermined weight ranges [see Dosage and Administration (2.6) ] . 2.2 Recommended TECVAYLI Dosage In Combination with Daratumumab and Hyaluronidase-fihj The recommended dosing schedule for TECVAYLI in combination with subcutaneous daratumumab and hyaluronidase-fihj is provided in Table 1. TECVAYLI should be administered until disease progression or unacceptable toxicity. Table 1: TECVAYLI Dosage Schedule in Combination with Daratumumab and Hyaluronidase-fihj Dosing schedule Week/Day TECVAYLI Dosage See Table 3 for recommendations on restarting TECVAYLI after dose delays. Concomitant Therapy Day 0 N/A Daratumumab and hyaluronidase-fihj Step-up dosing schedule The Step-up dosing schedule is a component of the recommended TECVAYLI dosage but is not applicable for the daratumumab and hyaluronidase-fihj dosing. Day 1 Step-up dose 1 (0.06 mg/kg) Step-up dose 1 must be administered 20 hours or more after the daratumumab and hyaluronidase-fihj dose. N/A Day 3 Step-up dose 2 (0.3 mg/kg) Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and if adverse reactions occur, step-up dose 2 may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions. N/A Day 7 First treatment dose (1.5 mg/kg) First treatment dose (1.5 mg/kg) may be given between 2 to 4 days after step-up dose 2 and if adverse reactions occur, first full treatment dose may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions. , Administer TECVAYLI at least 3 hours after the daratumumab and hyaluronidase-fihj dose for the first treatment dose. For subsequent doses, administer TECVAYLI at least 15 minutes after the daratumumab and hyaluronidase-fihj dose. Daratumumab and hyaluronidase-fihj Weekly dosing schedule Weeks 2 to 8 1.5 mg/kg once weekly , Maintain a minimum of 5 days between 1.5 mg/kg once weekly doses. Daratumumab and hyaluronidase-fihj once weekly Biweekly (every two weeks) dosing schedule Weeks 9 to 24 3 mg/kg every two weeks , Maintain a minimum of 12 days between 3 mg/kg every two weeks doses. Daratumumab and hyaluronidase-fihj every two weeks Every four weeks dosing schedule Week 25 onwards 3 mg/kg every four weeks , Maintain a minimum of 25 days between 3 mg/kg every four weeks doses. Daratumumab and hyaluronidase-fihj every four weeks For dosage and administration instructions for daratumumab and hyaluronidase-fihj, see Clinical Studies (14.1) and refer to daratumumab and hyaluronidase-fihj monotherapy Prescribing Information. Monotherapy The recommended dosing schedule for TECVAYLI monotherapy is provided in Table 2. TECVAYLI should be administered until disease progression or unacceptable toxicity. Table 2: TECVAYLI Dosage Schedule for Monotherapy Dosing schedule Day Dosage All Patients Step-up dosing schedule See Table 3 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.4) ] . Day 1 Step-up dose 1 0.06 mg/kg Day 4 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. Step-up dose 2 0.3 mg/kg Day 7 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. First treatment dose 1.5 mg/kg Weekly dosing schedule One week after first treatment dose and once weekly thereafter Maintain a minimum of 5 days between 1.5 mg/kg once weekly doses 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. Maintain a minimum of 12 days between 1.5 mg/kg every two week doses 2.3 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 Tables 1 and 2 ), 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) Administration of pretreatment medications may be required prior to administration of subsequent doses of TECVAYLI in patients who: Repeat doses within the TECVAYLI step-up dosing schedule following a dose delay [see Dosage and Administration (2.4) ]. Experienced CRS following the prior dose of TECVAYLI [see Dosage and Administration (2.5) ]. Prophylaxis for Herpes Zoster Reactivation Prior to starting treatment with TECVAYLI, consider initiation of antiviral prophylaxis to prevent herpes zoster reactivation per guidelines. 2.4 Restarting TECVAYLI after Dosage Delay If a dose of TECVAYLI is delayed, restart therapy based on the recommendations in Table 3 and resume the treatment schedule accordingly [see Dosage and Administration (2.2) ] . Administer pretreatment medications as indicated in Table 3 [see Dosage and Administration (2.3) ]. Table 3: Recommendations for Restarting Therapy with TECVAYLI After Dose Delay Last dose administered Time since the last dose administered Action Step-up dose 1 More than 7 days Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer pretreatment medications prior to TECVAYLI dose and monitor patients accordingly [see Dosage and Administration (2.3 , 2.5) ] . 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. More than 28 days Consider benefit-risk of restarting TECVAYLI in patients who require a dose delay of more than 28 days due to an adverse reaction. Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Weekly treatment dose 28 days or less Continue TECVAYLI 1.5 mg/kg once weekly. 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) or every four weeks treatment dose 63 days or less Continue TECVAYLI at last dose given every two weeks or every four weeks schedule. 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). 2.5 Dosage Modifications for Adverse Reactions Dosage reductions of TECVAYLI are not recommended. Refer to daratumumab and hyaluronidase-fihj Prescribing Information for information about dosage modifications for daratumumab and hyaluronidase-fihj. Dosage delays may be required to manage toxicities related to TECVAYLI [see Warnings and Precautions (5) ]. See Tables 4 , 5 and 6 for recommended actions for adverse reactions of CRS, neurologic toxicity, and ICANS. See Table 7 for recommended actions for other adverse reactions following administration of TECVAYLI. Management of CRS, Neurologic Toxicity, and ICANS Cytokine Release Syndrome Management recommendations for cytokine release syndrome (CRS) are summarized in Table 4. 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 4 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 4: Recommendations for Management of Cytokine Release Syndrome Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS. Presenting Symptoms Actions Grade 1 Temperature ≥100.4 °F (38 °C) 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. Withhold TECVAYLI until CRS resolves. 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 Low-flow nasal cannula is ≤6 L/minute, and high-flow nasal cannula is >6 L/minute. or blow-by. Withhold TECVAYLI until CRS resolves. Administer pretreatment medications prior to next dose of TECVAYLI. See Table 3 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.4) ] . Monitor patients for 48 hours following the next TECVAYLI dose. Instruct patients to remain within proximity of a healthcare facility during daily monitoring and consider hospitalization. [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 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 and 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 drugs for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Table 7: Recommended TECVAYLI Dosage Modifications for Other Adverse Reactions Adverse Reactions Severity Actions Infections Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. [see Warnings and Precautions (5.5) ] All Grades Withhold TECVAYLI in patients with active infection during the step-up dosing schedule. See Table 3 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.4) ] . Grade 3 Withhold subsequent TECVAYLI 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 TECVAYLI 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 (ANC) < 0.5 × 10 9 /L Withhold TECVAYLI until ANC is ≥ 0.5 × 10 9 /L. Febrile neutropenia Withhold TECVAYLI until ANC is ≥1 × 10 9 /L and fever resolves. Hemoglobin < 8 g/dL Withhold TECVAYLI until hemoglobin is ≥8 g/dL. Monotherapy: Platelet count < 25,000/mcL or platelet count between 25,000/mcL and 50,000/mcL with bleeding Combination therapy: Platelet count < 50,000/mcL Monotherapy: Withhold TECVAYLI until platelet count is ≥ 25,000/mcL and no evidence of bleeding. Combination therapy: Withhold TECVAYLI until platelet count is ≥ 50,000/mcL 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 TECVAYLI doses administered after TECVAYLI step-up dosing schedule until adverse reaction improves to Grade 1 or less. 2.6 Preparation and Administration TECVAYLI is 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 8, 9, 10 and 11 below to determine the dosage based on predetermined weight ranges. 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 1 using TECVAYLI 30 mg/3 mL (10 mg/mL) vial. Table 8: Step-up Dose 1 (0.06 mg/kg) Injection Volumes and Number of Vials 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 39.9 2.2 0.22 1 40 to 44.9 2.5 0.25 1 45 to 49.9 2.8 0.28 1 50 to 59.9 3.3 0.33 1 60 to 69.9 3.9 0.39 1 70 to 79.9 4.5 0.45 1 80 to 89.9 5.1 0.51 1 90 to 99.9 5.7 0.57 1 100 to 109.9 6.3 0.63 1 110 to 119.9 6.9 0.69 1 120 to 129.9 7.5 0.75 1 130 to 139.9 8.1 0.81 1 140 to 149.9 8.7 0.87 1 150 to 160 9.3 0.93 1 Use Table 9 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 9: Step-up Dose 2 (0.3 mg/kg) Injection Volumes and Number of Vials 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 39.9 11 1.1 1 40 to 44.9 13 1.3 1 45 to 49.9 14 1.4 1 50 to 59.9 16 1.6 1 60 to 69.9 19 1.9 1 70 to 79.9 22 2.2 1 80 to 89.9 25 2.5 1 90 to 99.9 28 2.8 1 100 to 109.9 31 3.1 2 110 to 119.9 34 3.4 2 120 to 129.9 37 3.7 2 130 to 139.9 40 4 2 140 to 149.9 43 4.3 2 150 to 160 47 4.7 2 Use Table 10 to determine total dose, injection volume and number of vials required based on patient's actual body weight for the 1.5 mg/kg dose using TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial. Table 10: 1.5 mg/kg Dose Injection Volumes and Number of Vials 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 39.9 56 0.62 1 40 to 44.9 64 0.71 1 45 to 49.9 71 0.79 1 50 to 59.9 83 0.92 1 60 to 69.9 99 1.1 1 70 to 79.9 108 1.2 1 80 to 89.9 126 1.4 1 90 to 99.9 144 1.6 1 100 to 109.9 153 1.7 1 110 to 119.9 171 1.9 2 120 to 129.9 189 2.1 2 130 to 139.9 198 2.2 2 140 to 149.9 216 2.4 2 150 to 160 234 2.6 2 Use Table 11 to determine total dose, injection volume and number of vials required based on patient's actual body weight for the 3 mg/kg dose using TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial. Table 11: 3 mg/kg Dose Injection Volumes and Number of Vials 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 39.9 108 1.2 1 40 to 44.9 126 1.4 1 45 to 49.9 144 1.6 1 50 to 59.9 162 1.8 2 60 to 69.9 198 2.2 2 70 to 79.9 225 2.5 2 80 to 89.9 252 2.8 2 90 to 99.9 288 3.2 2 100 to 109.9 315 3.5 3 110 to 119.9 342 3.8 3 120 to 129.9 378 4.2 3 130 to 139.9 405 4.5 3 140 to 149.9 432 4.8 3 150 to 160 468 5.2 4 Remove the appropriate strength TECVAYLI vial(s) 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. 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 that require greater than 2 mL equally into multiple syringes. Use TECVAYLI 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 needed, administer injections 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. Storage and Disposal 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. Dispose of any unused product or waste material in accordance with local requirements.

See official label

1 INDICATIONS AND USAGE TECVAYLI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.