Standard Dose
2 DOSAGE AND ADMINISTRATION LUNSUMIO and LUNSUMIO VELO have different dosage and administration instructions. Administer LUNSUMIO only as an intravenous infusion. ( 2.1 ) Premedicate to reduce risk of CRS and infusion-related reactions. ( 2.3 , 5.1 ) Recommended dosage for LUNSUMIO for intravenous infusion ( 2.2 ): Day of Treatment Cycle length = 21 days Intravenous Dose of LUNSUMIO Rate of Infusion Cycle 1 Day 1 1 mg Administer over a minimum of 4 hours. Day 8 2 mg Day 15 60 mg Cycle 2 Day 1 60 mg Administer over 2 hours if infusions from Cycle 1 were well-tolerated. Cycles 3+ Day 1 30 mg See Full Prescribing Information for instructions on preparation and administration. ( 2.5 ) 2.1 Important Dosing Information LUNSUMIO and LUNSUMIO VELO have different dosage and administration instructions [see Dosage and Administration (2.2) and Warnings and Precautions (5.7) ]. LUNSUMIO is for intravenous use only. Check the product label to ensure that the correct formulation (LUNSUMIO or LUNSUMIO VELO) is being prescribed and administered. Do not substitute LUNSUMIO for or with LUNSUMIO VELO. Administer LUNSUMIO to well-hydrated patients. Premedicate before each dose in Cycle 1 and Cycle 2 [see Dosage and Administration (2.3) ] . Administer only as an intravenous infusion through a dedicated infusion line. Do not use an in-line filter to administer LUNSUMIO . Drip chamber filters can be used to administer LUNSUMIO. LUNSUMIO should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 and 5.2) ] . 2.2 Recommended Dosage The recommended dosage for LUNSUMIO intravenous infusion is presented in Table 1 . Administer for 8 cycles, unless patients experience unacceptable toxicity or disease progression. For patients who achieve a complete response, no further treatment beyond 8 cycles is required. For patients who achieve a partial response or have stable disease in response to treatment with LUNSUMIO after 8 cycles, an additional 9 cycles of treatment (17 cycles total) should be administered, unless a patient experiences unacceptable toxicity or disease progression. Table 1. Recommended Dose and Schedule of LUNSUMIO Intravenous Infusion (21-Day Treatment Cycles) Day of Treatment Intravenous Dose of LUNSUMIO Rate of Infusion Cycle 1 Day 1 1 mg Administer over a minimum of 4 hours. Day 8 2 mg Day 15 60 mg Cycle 2 Day 1 60 mg Administer over 2 hours if infusions from Cycle 1 were well-tolerated. Cycles 3+ Day 1 30 mg Table 2. Recommendations for Restarting Therapy with LUNSUMIO Intravenous Infusion After Dose Delay Last Intravenous Dose Administered Time Since Last Dose Administered Action for Next Intravenous Dose(s) 1 mg Cycle 1 Day 1 1week to 2 weeks Administer 2 mg (Cycle 1 Day 8), then resume the planned treatment schedule. Greater than 2 weeks Repeat 1 mg (Cycle 1 Day 1), then administer 2 mg (Cycle 1 Day 8) and resume the planned treatment schedule. 2 mg Cycle 1 Day 8 1 week to 2 weeks Administer 60 mg (Cycle 1 Day 15), then resume the planned treatment schedule. Greater than 2 weeks to less than 6 weeks Repeat 2 mg (Cycle 1 Day 8), then administer 60 mg (Cycle 1 Day 15) and resume the planned treatment schedule. Greater than or equal to 6 weeks Repeat 1 mg (Cycle 1 Day 1) and 2 mg (Cycle 1 Day 8), then administer 60 mg (Cycle 1 Day 15) and resume the planned treatment schedule. 60 mg Cycle 1 Day 15 1 week to less than 6 weeks Administer 60 mg (Cycle 2 Day 1), then resume the planned treatment schedule. Greater than or equal to 6 weeks Repeat 1 mg (Cycle 2 Day 1) and 2 mg (Cycle 2 Day 8), then administer 60 mg (Cycle 2 Day 15), followed by 30 mg (Cycle 3 Day 1) and then resume the planned treatment schedule. 60 mg Cycle 2 Day 1 3 weeks to less than 6 weeks Administer 30 mg (Cycle 3 Day 1), then resume the planned treatment schedule. Greater than or equal to 6 weeks Repeat 1 mg (Cycle 3 Day 1) and 2 mg (Cycle 3 Day 8), then administer 30 mg (Cycle 3 Day 15) For the Day 1, Day 8, and Day 15 doses in the next cycle, administer premedication as per Table 3 for all patients. , followed by 30 mg (Cycle 4 Day 1) and then resume the planned treatment schedule. 30 mg Cycle 3 onwards 3 weeks to less than 6 weeks Administer 30 mg, then resume the planned treatment schedule. Greater than or equal to 6 weeks Repeat 1 mg on Day 1 and 2 mg on Day 8 during the next cycle, then administer 30 mg on Day 15 , followed by 30 mg on Day 1 of subsequent cycles. 2.3 Recommended Premedication Premedication to reduce the risk of CRS and infusion-related reactions are outlined in Table 3 [see Warnings and Precautions (5.1) ] . Table 3. Premedication to be Administered to Patients Prior to LUNSUMIO Intravenous Infusion Treatment Cycle Patients Requiring Premedication Premedication Dosage Administration Cycle 1 and Cycle 2 All patients Corticosteroid Dexamethasone 20 mg (preferred) intravenous or methylprednisolone 80 mg intravenous Complete at least 1 hour prior to infusion Antihistamine Diphenhydramine hydrochloride 50 mg to 100 mg or equivalent oral or intravenous antihistamine At least 30 minutes prior to infusion Antipyretic Oral acetaminophen (500 mg to 1,000 mg) At least 30 minutes prior to infusion Cycles 3+ Patients who experienced any grade CRS with the previous dose Corticosteroid Dexamethasone 20 mg (preferred) intravenous or methylprednisolone 80 mg intravenous Complete at least 1 hour prior to infusion Antihistamine Diphenhydramine hydrochloride 50 mg to 100 mg or equivalent oral or intravenous antihistamine At least 30 minutes prior to infusion Antipyretic Oral acetaminophen (500 mg to 1,000 mg) At least 30 minutes prior to infusion 2.4 Dosage Modifications for Adverse Reactions See Tables 4 and 5 for the recommended dosage modifications for adverse reactions of CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). See Table 6 for the recommended dosage modifications for other adverse reactions following administration of LUNSUMIO. Dosage Modifications for Cytokine Release Syndrome Identify CRS based on clinical presentation [see Warnings and Precautions (5.1) ] . Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold LUNSUMIO until CRS resolves, manage according to the recommendations in Table 4 and per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Table 4. Recommendations for Management of Cytokine Release Syndrome with LUNSUMIO Intravenous Infusion Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS. Presenting Symptoms Actions If CRS is refractory to management, consider other causes including hemophagocytic lymphohistiocytosis [see Warnings and Precautions (5.4) ] . Grade 1 Fever ≥ 100.4°F (38°C) Premedication may mask fever, therefore if clinical presentation is consistent with CRS, follow these management guidelines. Withhold current infusion of LUNSUMIO and manage per current practice guidelines. If symptoms resolve, restart infusion at the same rate. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO. Refer to Table 2 for information on restarting LUNSUMIO after dose delays [see Dosage and Administration (2.2) ] . Administer premedication Refer to Table 3 for additional information on premedication. prior to next dose of LUNSUMIO and monitor patient more frequently. Grade 2 Fever ≥ 100.4°F (38°C) with: Hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen Low-flow oxygen defined as oxygen delivered at < 6 L/minute; high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute. by nasal cannula or blow-by. Withhold current infusion of LUNSUMIO and manage per current practice guidelines. If symptoms resolve, restart infusion at 50% rate. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO. Administer premedication prior to next dose of LUNSUMIO and consider infusing the next dose at 50% rate. For the next dose of LUNSUMIO, monitor more frequently and consider hospitalization. Recurrent Grade 2 CRS Manage per Grade 3 CRS. Grade 3 Fever ≥ 100.4°F (38°C) with: Hypotension requiring a vasopressor (with or without vasopressin) and/or hypoxia requiring high flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask. Withhold LUNSUMIO, manage per current practice guidelines and provide supportive therapy, which may include intensive care. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO. Administer premedication prior to next dose of LUNSUMIO and infuse the next dose at 50% rate. Hospitalize for the next dose of LUNSUMIO. Recurrent Grade 3 CRS Permanently discontinue LUNSUMIO. Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care. Grade 4 Fever ≥ 100.4°F (38°C) with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation). Permanently discontinue LUNSUMIO. Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care. Dosage Modifications for Neurologic Toxicity, including ICANS Management recommendations for neurologic toxicity, including ICANS, are summarized in Table 5 . At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding of LUNSUMIO based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care. Table 5. Recommendations for Management of Neurologic Toxicity (including ICANS) Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. , Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. Actions Neurologic Toxicity (including ICANS ) Grade 1 Continue LUNSUMIO and monitor neurologic toxicity symptoms. If ICANS, manage per current practice guidelines. Grade 2 Withhold LUNSUMIO until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours. See Table 2 for recommendations on restarting LUNSUMIO after dose delays [see Dosage and Administration (2.2) ] . Provide supportive therapy, and consider neurologic evaluation. If ICANS, manage per current practice guidelines. Grade 3 Withhold LUNSUMIO until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours. Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. If recurrence of ICANS, permanently discontinue LUNSUMIO. Grade 4 Permanently discontinue LUNSUMIO. Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. Other Adverse Reactions Table 6. Recommended Dosage Modification for Other Adverse Reactions Adverse Reactions Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. Severity Actions Infections [see Warnings and Precautions (5.3) ] Grades 1 – 4 Withhold LUNSUMIO in patients with active infection until the infection resolves. See Table 2 for recommendations on restarting LUNSUMIO after dose delays [see Dosage and Administration (2.2) ] . For Grade 4, consider permanent discontinuation of LUNSUMIO. Neutropenia [see Warnings and Precautions (5.4) ] Absolute neutrophil count less than 0.5 × 10 9 /L Withhold LUNSUMIO until absolute neutrophil count is 0.5 × 10 9 /L or higher. Other Adverse Reactions [see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ] Grade 3 or higher Withhold LUNSUMIO until the toxicity resolves to Grade 1 or baseline. 2.5 Preparation and Administration To prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is LUNSUMIO for intravenous infusion. A peel-off label is provided on the LUNSUMIO Prescribing Information that should be attached to the final prepared solution. Remove the peel-off label from the Prescribing Information in the LUNSUMIO carton before discarding the carton. Affix the peel-off label to the diluted LUNSUMIO infusion bag. Preparation Use aseptic technique to prepare LUNSUMIO. Inspect the vial visually for any particulate matter, prior to administration. Do not use if the solution is discolored, or cloudy, or if foreign particles are present. Determine the dose, the total volume of LUNSUMIO solution required, and the number of LUNSUMIO vials needed. Dilution 1. Withdraw the volume from an infusion bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection, USP equal to the volume of the LUNSUMIO required for the patient's dose and discard. Only use infusion bags made of polyvinyl chloride (PVC) or polyolefin (PO) such as polyethylene (PE) and polypropylene (PP). 2. Withdraw the required volume of LUNSUMIO from the vial using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection, USP according to Table 7 . Discard any unused portion left in the vial. Table 7. Dilution of LUNSUMIO Dose of LUNSUMIO Volume of LUNSUMIO Size of 0.9% or 0.45% Sodium Chloride Injection Infusion Bag 1 mg 1 mL 50 mL or 100 mL 2 mg 2 mL 50 mL or 100 mL 60 mg 60 mL 100 mL or 250 mL 30 mg 30 mL 50 mL, 100 mL, or 250 mL 3. Gently mix the intravenous bag by slowly inverting the bag. Do not shake. 4. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if visibly opaque particles, discoloration, or foreign particles are observed. 5. Apply the peel-off label from the Prescribing Information to the infusion bag. 6. Immediately use diluted LUNSUMIO infusion solution. If not used immediately, the diluted solution can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours and at ambient temperature 9°C to 30°C (48°F to 86°F) for up to 16 hours. Prior to administration, ensure the infusion solution comes to reach room temperature. Administration Administer LUNSUMIO as an intravenous infusion only. Do not use an in-line filter to administer LUNSUMIO . Do not mix LUNSUMIO with, or administer through the same infusion line, as other medicinal products. No incompatibilities have been observed with infusion sets or infusion aids with product contacting materials of PVC, PE, polyurethane (PUR), polybutadiene (PBD), silicone, acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyetherurethane (PEU), fluorinated ethylene propylene (FEP), or polytetrafluorethylene (PTFE), or with drip chamber filter membrane composed of polyamide (PA).