TECVAYLI

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. as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. TECVAYLI is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager 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 ( 1 ). as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody ( 1 ).

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 <48 Hours: Withhold TECVAYLI until CRS resolves. Provide supportive therapy, which may include intensive care. Administer pretreatment medications prior to next TECVAYLI dose. Patients should be hospitalized for 48 hours following the next TECVAYLI dose . 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 Immune Effector Cell-Associated Neurotoxicity Syndrome Management recommendations for neurologic toxicity and immune effector cell-associated neurotoxicity syndrome (ICANS) are summarized in Tables 5 and 6. 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 6 and consider further management per current practice guidelines. Table 5: Recommendations for Management of Neurologic Toxicity (excluding ICANS) Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI- CTCAE), version 4.03. Actions Grade 1 Withhold TECVAYLI until neurologic toxicity symptoms resolve or stabilize. See Table 3 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.4) ] . 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 6: Recommendations for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. Presenting Symptoms Management is determined by the most severe reaction, not attributable to any other cause. Actions Grade 1 ICE score 7–9 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. , or depressed level of consciousness Not attributable to any other cause. : awakens spontaneously. Withhold TECVAYLI until ICANS resolves. See Table 3 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.4) ]. 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. Grade 2 ICE score 3–6 , or depressed level of consciousness : awakens to voice. Withhold TECVAYLI until ICANS resolves. Administer dexamethasone All references to dexamethasone administration are for dexamethasone or equivalent. 10 mg intravenously every 6 hours and 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 drugs for seizure prophylaxis. 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 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 and 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 drugs for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Patients should be hospitalized for 48 hours following the next TECVAYLI dose. Recurrent Grade 3 ICANS: 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. 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. 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 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.

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Hepatotoxicity : Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity ( 2.5 , 5.4 ) Infections : Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. ( 2.5 , 5.5 ) Neutropenia : Monitor complete blood cell counts at baseline and periodically during treatment. Withhold TECVAYLI based on severity. ( 2.5 , 5.6 ) Hypersensitivity and Other Administration Reactions : Can cause systemic administration-related reactions and local injection site reactions. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. ( 2.5 , 5.7 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.8 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . In the clinical trials (monotherapy and combination therapy trials; N=448), CRS occurred in 64% of patients who received TECVAYLI at the recommended dosage, with Grade 1 CRS occurring in 46% of patients, Grade 2 in 18%, and Grade 3 in 0.2%. Recurrent CRS occurred in 27% of patients. Most patients experienced CRS during the initial step-up dosing schedule (step-up dose 1 (37%), step-up dose 2 (32%), or the initial treatment dose (20%)). CRS first occurred following subsequent doses of TECVAYLI in 2.5% of patients. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose and the median duration of CRS was 2 (range: 1 to 22) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation). Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.1 , 2.5) ] . Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly [see Dosage and Administration (2.3 , 2.5) ] . At the first sign of CRS, immediately evaluate the patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold until CRS resolves or permanently discontinue TECVAYLI based on severity [see Dosage and Administration (2.5) ] . TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ]. 5.2 Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome TECVAYLI can cause serious, life-threatening or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Adverse Reactions (6.1) ] . In the clinical trials (monotherapy and combination therapy trials; N=448), neurologic toxicity occurred in 60% of patients who received TECVAYLI at the recommended dosage, with Grade 3 or 4 neurologic toxicity in 6%. Neurologic toxicities reported in ≥5% of patients included headache (27%), sensory neuropathy (16%), motor dysfunction (15%), insomnia (12%), encephalopathy (11%), and dizziness (8%). Fatal neurologic toxicity occurred in 0.4% of patients, including Guillain-Barré syndrome and status epilepticus (one patient each). In MajesTEC-1, ICANS was reported in 6% of patients who received TECVAYLI as monotherapy at the recommended dosage [see Adverse Reactions (6.1) ] . Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent TECVAYLI doses. The median time to onset of ICANS was 4 days (range: 2 to 8 days) after the most recent TECVAYLI dose with a median duration of 3 days (range: 1 to 20 days). The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. In MajesTEC-3, ICANS was reported in 1.1% of patients who received the recommended TECVAYLI dosage in combination with daratumumab and hyaluronidase-fihj, including Grade 4 ICANS in 1 patient. All events of ICANS occurred during the step-up dosing schedule [see Adverse Reactions (6.1) ] . The median time to onset of ICANS was 2 days (range: 1 to 3 days) after the most recent dose and the median duration of ICANS was 2 days (range: 1 to 2 days). The clinical manifestations of ICANS reported were amnesia, encephalopathy and delirium. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during TECVAYLI treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold until neurologic toxicity resolves or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines [see Dosage and Administration (2.5) ] . Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness [see Adverse Reactions (6.1) ] . Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves [see Dosage and Administration (2.1) ] . TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ]. 5.3 TECVAYLI and TALVEY REMS TECVAYLI is available only through a restricted program under a REMS called the "TECVAYLI and TALVEY REMS" because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2) ]. Notable requirements of the TECVAYLI and TALVEY REMS include the following: Prescribers must be certified with the REMS by enrolling and completing training. Prescribers must counsel patients receiving TECVAYLI about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with Patient Wallet Card. Pharmacies and healthcare settings that dispense TECVAYLI must be certified with this REMS and must verify prescribers are certified through this REMS. Wholesalers and distributers must only distribute TECVAYLI to certified pharmacies or healthcare settings. Further information about the "TECVAYLI and TALVEY REMS" is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064. 5.4 Hepatotoxicity TECVAYLI can cause hepatotoxicity, including fatalities. There was one fatal case of hepatic failure in MajesTEC-1. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), elevated aspartate aminotransferase (AST) occurred in 47% of patients, with Grade 3 or 4 elevations in 2.9%. Elevated alanine aminotransferase (ALT) occurred in 48% of patients, with Grade 3 or 4 elevations in 3.8%. Elevated total bilirubin occurred in 10% of patients with Grade 3 or 4 elevations in 0.7%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during TECVAYLI treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.5) ]. 5.5 Infections TECVAYLI can cause severe, life-threatening, or fatal infections. In MajesTEC-1 (N=165), in patients who received the recommended TECVAYLI dosage, serious infections, including opportunistic infections, occurred in 30% of patients, Grade 3 or 4 infections occurred in 35% of patients, and fatal infections occurred in 4.2% of patients [see Adverse Reactions (6.1) ] . In MajesTEC-3 (N=283), in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj at the recommended dosage, serious infections, including opportunistic infections, occurred in 54% of patients, Grade 3 or Grade 4 infections occurred in 54% of patients and fatal infections occurred in 4.6% of patients [see Adverse Reactions (6.1) ] . Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to current practice guidelines [see Dosage and Administration (2.3) ] . Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.5) ] . Monitor immunoglobulin levels prior to and during treatment with TECVAYLI and administer subcutaneous or intravenous immunoglobulin (IVIG) to maintain the serum levels >400 mg/dL. 5.6 Neutropenia TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), decreased neutrophils occurred in 88% of patients, with Grade 3 or 4 decreased neutrophils in 70%. Febrile neutropenia occurred in 6% of patients [see Adverse Reactions (6.1) ]. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity [see Dosage and Administration (2.5) ] . 5.7 Hypersensitivity and Other Administration Reactions TECVAYLI can cause both systemic administration-related reactions and local injection-site reactions. Systemic Reactions In patients who received the recommended TECVAYLI dosage in the clinical trials (monotherapy and combination therapy trials; N=448), 2.5% of patients experienced systemic-administration reactions, which included recurrent pyrexia and rash. Local Reactions In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), injection-site reactions occurred in 37% of patients with Grade 1 injection-site reactions in 29% and Grade 2 in 9%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.5) ] . 5.8 Embryo-Fetal Toxicity Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient. Advise pregnant patients of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .

7 DRUG INTERACTIONS TECVAYLI causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of certain cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates, which may increase the risk of adverse reactions of the CYP substrates. The highest risk of drug-drug interaction is expected to occur after initiation of TECVAYLI step-up dosing schedule up to 7 days after the first treatment dose and during and after CRS [see Warnings and Precautions (5.1) ] . Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate as needed. Certain CYP Substrates : Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate, as needed ( 7 ).

6 ADVERSE REACTIONS The following adverse reactions are also described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity including ICANS [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Neutropenia [see Warnings and Precautions (5.6) ] Hypersensitivity and Other Administration Reactions [see Warnings and Precautions (5.7) ] The most common adverse reactions (≥20%) in patients who received TECVAYLI monotherapy are pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. ( 6.1 ) The most common adverse reactions (≥20%) in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj are hypogammaglobulinemia, upper respiratory tract infection, cytokine release syndrome, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis and weight decreased. ( 6.1 ) The most common Grade 3 to 4 laboratory abnormalities (≥20%) with TECVAYLI (as monotherapy or in combination with daratumumab and hyaluronidase-fihj) are decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed/Refractory Multiple Myeloma In Combination with Daratumumab and Hyaluronidase-fihj The safety of TECVAYLI in combination with daratumumab and hyaluronidase-fihj (N=283) compared with either daratumumab and hyaluronidase-fihj, pomalidomide and dexamethasone (DPd) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) (N=290) was evaluated in patients with relapsed or refractory multiple myeloma in MajesTEC-3 [see Clinical Studies (14.1) ] . Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg once weekly, followed by TECVAYLI 3 mg/kg every two weeks, followed by TECVAYLI 3 mg/kg every four weeks, subcutaneously. Among patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj the median exposure was 32 (range 0.03 to 43) months. Among patients who received DPd or DVd the median exposure was 16 (range 0.03 to 45) months. Serious adverse reactions occurred in 71% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj. Serious adverse reactions reported in ≥3% of patients included pneumonia (33%), upper respiratory tract infection (15%), cytokine release syndrome (10%), COVID-19 (7%), sepsis (6%), second primary malignancy (5%), pyrexia (4.9%), febrile neutropenia (4.6%), and gastroenteritis (4.2%). Fatal adverse reactions occurred in 2.5% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj, and included sepsis (0.7%), pneumonia (0.4%), sudden death (0.4%), myocardial infarction (0.4%), enterovirus myocarditis (0.4%) and hemophagocytic lymphohistiocytosis (0.4%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 6% of patients. Adverse reactions leading to discontinuation of TECVAYLI in more than one patient were pneumonia (1.1%), diarrhea (0.7%), fatigue (0.7%), second primary malignancy (0.7%), upper respiratory tract infection (0.7%) and cough (0.7%). Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 94% of patients. Adverse reactions which required dosage interruption of TECVAYLI in ≥5% of patients included neutropenia (53%), upper respiratory tract infection (48%), COVID-19 (34%), pneumonia (34%), thrombocytopenia (14%), cytokine release syndrome (13%), gastroenteritis (10%), cough (10%), pyrexia (8%), diarrhea (7%), sepsis (6%) and fatigue (5%). The most common adverse reactions (≥20%) were hypogammaglobulinemia, upper respiratory tract infection, cytokine release syndrome, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and weight decreased. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells and decreased platelets. Table 12 summarizes the adverse reactions in MajesTEC-3. Table 12: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received TECVAYLI in Combination with Daratumumab and Hyaluronidase-fihj in MajesTEC-3 Adverse Reaction TECVAYLI with daratumumab and hyaluronidase-fihj (N=283) DPd or DVd (N=290) Any Grade (%) Grade 3 or 4 (%) Any Grade (%) Grade 3 or 4 (%) DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone. Adverse reactions were graded according to NCI-CTCAE Version 5.0, with the exception of ICANS and CRS, which were graded by ASTCT 2019 consensus grading system; adverse reactions that were considered symptoms of CRS or ICANS were not included. Immune system disorders Hypogammaglobulinemia Hypogammaglobulinemia includes hypogammaglobulinemia, hypoglobulinemia; and/or patients with laboratory IgG levels below 400 mg/dL following treatment with TECVAYLI. 84 6 60 1.4 Cytokine release syndrome 60 0 0 0 Infections Upper respiratory tract infection Upper respiratory tract infection includes bronchitis, bronchiolitis, pharyngitis, rhinitis, sinusitis, sinobronchitis, tracheitis, and tracheobronchitis and other related terms. 79 17 62 13 COVID-19 Includes other related terms. 45 6 33 2.1 Pneumonia Pneumonia includes atypical pneumonia, bacterial pneumonia, fungal pneumonia, viral pneumonia, and other related terms. Includes the following fatal adverse reactions: Tec-Dara: Pneumonia (n=1); DPd/DVd: Pneumonia (n=2). 42 33 35 28 Gastroenteritis 20 4.9 8 0.7 Urinary tract infection 17 2.8 13 1 Herpes virus infection 11 2.1 6 0.3 Respiratory, thoracic and mediastinal disorders Cough 53 0.7 24 0 Dyspnea 13 1.8 20 2.1 Gastrointestinal disorders Diarrhea 52 3.9 31 2.4 Nausea 23 0 12 0.3 Vomiting 17 0 7 0 Abdominal pain 16 0.7 13 0 Constipation 14 0 20 0.3 Musculoskeletal and connective tissue disorders Musculoskeletal pain 50 1.4 47 4.5 General disorders and administration site conditions Injection site reaction Includes injection site reactions related to teclistamab, daratumumab and hyaluronidase-fihj, or bortezomib. 41 0 4.5 0 Fatigue 39 3.9 40 4.1 Pyrexia 37 1.4 19 0.3 Edema 13 0.4 22 0.3 Nervous system disorders Headache 26 1.4 12 0.3 Sensory neuropathy Sensory neuropathy includes dysaesthesia, hyperaesthesia, hypoaesthesia, paraesthesia, neuralgia, peripheral neuropathy, polyneuropathy, sciatica and other related terms. 17 0.7 25 0.3 Motor dysfunction Motor dysfunction includes balance disorder, dysarthria, dysphonia, gait disturbance, muscle contracture, muscle spasms, muscle spasticity, muscle twitching, muscular weakness, myopathy, peripheral motor neuropathy, tremor and other related terms. 14 0 30 1 Investigations Weight decreased 20 2.8 7 1.4 Metabolism and nutrition disorders Decreased appetite 19 1.1 7 0 Cardiac disorders Cardiac arrhythmia 11 1.1 8 2.1 Neoplasms Second primary malignancy 11 4.6 9 4.8 Vascular disorders Hypertension 11 4.6 6 2.4 Clinically relevant adverse reactions in <10% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj included sepsis, encephalopathy, CMV infection, febrile neutropenia and ICANS. Table 13 summarizes laboratory abnormalities in MajesTEC-3. Table 13: Select Laboratory Abnormalities (≥30%) that Worsened from Baseline in Patients with Multiple Myeloma who Received TECVAYLI in Combination with Daratumumab and Hyaluronidase-fihj in MajesTEC-3 Laboratory Abnormality TECVAYLI with daratumumab and hyaluronidase-fihj (N=283) DPd or DVd (N=290) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone. Percentages calculated with the number of subjects with a baseline and at least one post-treatment value for each lab test as denominator. Laboratory toxicity grades are derived based on NCI CTCAE Version 5.0. The denominator used to calculate the incidence varied from 137 to 282 in Tec-Dara and 135 to 289 in DPd/DVd based on the number of patients with a baseline value and at least one post-treatment value. Hematology Lymphocyte Count Decreased 99 95 93 64 White Blood Cell Decreased 94 60 96 74 Neutrophil Count Decreased 91 78 94 84 Platelet Count Decreased 73 21 72 25 Hemoglobin Decreased 64 17 61 19 Chemistry Alanine Aminotransferase Increased 60 5 33 2.4 Aspartate Aminotransferase Increased 55 3.9 22 1.7 Potassium Decreased 52 15 35 8 GGT Increased 51 5 24 0 Sodium Decreased 46 10 37 6 Lipase Increased 49 18 21 4.7 Serum Amylase Increased 31 7 13 0 Monotherapy The safety of TECVAYLI monotherapy (N=165) in patients with relapsed or refractory multiple myeloma was evaluated in MajesTEC-1 [see Clinical Studies (14.1) ] . Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg, subcutaneously once weekly. Among patients who received TECVAYLI, 47% were exposed for 6 months or longer and 7% were exposed for one year or longer. The median age of patients who received TECVAYLI was 64 years (range: 33 to 84 years); 58% were male; 81% were White, 13% were Black or African American, and 2% were Asian. Serious adverse reactions occurred in 54% of patients who received TECVAYLI. Serious adverse reactions in >2% of patients included pneumonia (15%), cytokine release syndrome (8%), sepsis (6%), general physical health deterioration (6%), COVID-19 (6%), acute kidney injury (4.8%), pyrexia (4.8%), musculoskeletal pain (2.4%), and encephalopathy (2.4%). Fatal adverse reactions occurred in 5% of patients who received TECVAYLI, including COVID-19 (1.8%), pneumonia (1.8%), septic shock (0.6%), acute renal failure (0.6%), and hemoperitoneum (0.6%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 1.2% of patients. Adverse reactions resulting in permanent discontinuation of TECVAYLI included pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia. Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 73% of patients. Adverse reactions which required dosage interruption in >5% of patients included neutropenia, pneumonia, pyrexia, cytokine release syndrome, upper respiratory tract infection, and COVID-19. The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. Table 14 summarizes the adverse reactions in MajesTEC-1. Table 14: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received TECVAYLI in MajesTEC-1 Adverse Reactions TECVAYLI (N=165) Any Grade (%) Grade 3 or 4 (%) Adverse reactions were graded based on NCI-CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria. General disorders and administration site conditions Pyrexia 76 3 Only grade 3 adverse reactions occurred. Injection site reaction Includes other related terms. 37 0.6 Fatigue 33 2.4 Chills 16 0 Pain 15 1.8 Edema 13 0 Immune system disorders Cytokine release syndrome 72 0.6 Hypogammaglobulinemia Hypogammaglobulinemia includes hypogammaglobulinemia and hypoglobulinemia. 11 1.2 Musculoskeletal and connective tissue disorders Musculoskeletal pain 44 4.2 Bone pain 16 3 Infections Upper respiratory tract infection Upper respiratory tract infection includes bronchitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, tracheitis and other related terms. 26 2.4 Pneumonia Pneumonia includes bacterial pneumonia, viral pneumonia, and other related terms. Includes the following fatal adverse reactions: hemorrhage (n=1), pneumonia (n=3). 24 15 Urinary tract infection 11 5 Gastrointestinal disorders Nausea 25 0.6 Diarrhea 21 2.4 Constipation 18 0 Vomiting 12 0.6 Nervous system disorders Headache 25 0.6 Motor dysfunction Motor dysfunction includes cogwheel rigidity, dysgraphia, dysphonia, gait disturbance, hypokinesia, muscle rigidity, muscle spasms, muscular weakness, peroneal nerve palsy, psychomotor hyperactivity, tremor and VI th nerve paralysis. 16 0 Sensory neuropathy Sensory neuropathy includes dysesthesia, hypoesthesia, hypoesthesia oral, neuralgia, paresthesia, paresthesia oral, peripheral sensory neuropathy, sciatica and vestibular neuronitis. 15 1.2 Encephalopathy Encephalopathy includes agitation, apathy, aphasia, confusional state, delirium, depressed level of consciousness, disorientation, dyscalculia, hallucination, lethargy, memory impairment, mental status changes and somnolence. 13 0 Vascular disorders Hypotension 18 1.2 Hemorrhage 12 1.8 Hypertension 12 4.8 Respiratory, thoracic, and mediastinal disorders Hypoxia 18 1.8 Cough 15 0 Cardiac disorders Cardiac arrhythmia 16 1.8 Metabolism and nutrition disorders Decreased appetite 11 0.6 Renal and urinary disorders Acute kidney injury 11 3.6 Clinically relevant adverse reactions in <10% of patients who received TECVAYLI included febrile neutropenia, sepsis, ICANS, seizure, Guillain-Barré syndrome, hepatic failure, and new onset or reactivated viral infections (including adenovirus, hepatitis B virus (HBV), cytomegalovirus (CMV), varicella zoster virus (VZV), herpes simplex virus (HSV), and progressive multifocal leukoencephalopathy (PML). Table 15 summarizes laboratory abnormalities in MajesTEC-1. Table 15: Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in TECVAYLI Treated Patients with Multiple Myeloma in MajesTEC-1 Laboratory Abnormality TECVAYLI (N=165 The denominator used to calculate the rate varied from 164 to 165 based on the number of patients with a baseline value and at least one post-treatment value. ) All Grades (%) Grade 3 or 4 (%) Laboratory toxicity grades are derived based on NCI CTCAE Version 4.03. Hematology Lymphocyte count decreased 92 84 White blood cell decreased 86 41 Neutrophil count decreased 84 56 Platelet count decreased 71 22 Hemoglobin decreased 67 33 Chemistry Albumin decreased 68 6 Alkaline phosphatase increased 42 2.4 Phosphorus decreased 38 13 Gamma-glutamyl transferase increased 37 8 Sodium decreased 35 10 Aspartate aminotransferase increased 34 1.2 Calcium (corrected) decreased 31 1.2 Creatinine increased 30 3

8.1 Pregnancy Risk Summary Based on the mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TECVAYLI in pregnant patients to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with TECVAYLI. Teclistamab-cqyv causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, teclistamab-cqyv has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. TECVAYLI is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.