Elrexfio Prescribing Information
• Cytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce the risk of CRS. Withhold ELREXFIO until CRS resolves or permanently discontinue based on severity[see2.2 Recommended DosageFor subcutaneous injection only.
The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24.
For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule.
For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule.Continue treatment with ELREXFIO until disease progression or unacceptable toxicity.
Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended
[see Dosage and Administration (2.3)].Table 1. ELREXFIO Dosing Schedule Note: See Table 2for recommendations on restarting ELREXFIO after dose delays. Dosing ScheduleDayELREXFIO DoseStep-up Dosing Schedule
Day 1Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose
[see Dosage and Administration (2.3)].Step-up dose 1
12 mg
Day 4
A minimum of 2 days should be maintained between step-up dose 1 (12 mg) and step-up dose 2 (32 mg).Step-up dose 2
32 mg
Day 8
A minimum of 3 days should be maintained between step-up dose 2 (32 mg) and the first treatment (76 mg) dose.First treatment dose
76 mg
Weekly Dosing Schedule
One week after first treatment dose and weekly thereafterA minimum of 6 days should be maintained between treatment doses.through week 24
Subsequent treatment doses
76 mg
Biweekly (Every 2 Week) Dosing Schedule
*Responders only week 25 onwardWeek 25 and every 2 weeks thereafter
through week 48Subsequent treatment doses
76 mg
Every 4 Week Dosing Schedule*In patients who have maintained the response following 24 weeks of treatment at the biweekly dosing scheduleWeek 49 and every 4 weeks thereafterSubsequent treatment doses76 mg,.),2.5 Dosage Modifications for Adverse ReactionsDosage reductions of ELREXFIO are not recommended.
Dosage delays may be required to manage toxicities related to ELREXFIO
[see Warnings and Precautions (5)]. Recommendations on restarting ELREXFIO after a dose delay are provided in Table 2.See Table 3and Table 4for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table 5for recommended actions for neurologic toxicity excluding ICANS and Table 6for recommended actions for other adverse reactions following administration of ELREXFIO. Consider further management per current practice guidelines.
Management of CRS, Neurologic Toxicity Including ICANSCytokine 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 ELREXFIO until CRS resolves. Manage CRS 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 CRS GradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS.Presenting SymptomsActionsGrade 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 anti-cytokine therapy.
• Withhold ELREXFIO until CRS resolves.See Table 2for recommendations on restarting ELREXFIO after dose delays.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 2
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension responsive to fluid and not requiring vasopressors, and/or• Oxygen requirement of low-flow nasal cannulaLow-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.or blow-by
• Withhold ELREXFIO until CRS resolves.• Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 3
(First occurrence)
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension requiring one vasopressor with or without vasopressin, and/or• Oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask
• Withhold ELREXFIO until CRS resolves.• Provide supportive therapy, which may include intensive care.• Patients should be hospitalized for 48 hours following the next dose of ELREXFIO.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 3 (Recurrent)
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension requiring one vasopressor with or without vasopressin, and/or• Oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask
• Permanently discontinue therapy with ELREXFIO.• Provide supportive therapy, which may include intensive care.
Grade 4
Temperature ≥100.4 °F (38 °C) with either:
• 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 therapy with ELREXFIO.• Provide supportive therapy, which may include intensive care.
Neurologic Toxicity Including ICANSManagement recommendations for ICANS and neurologic toxicity are summarized in Table 4 and Table 5.
At the first sign of neurologic toxicity, including ICANS, withhold ELREXFIO 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 4 and consider further management per current practice guidelines.Table 4. Recommendations for Management of ICANS GradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS.Presenting SymptomsManagement is determined by the most severe event, not attributable to any other cause.ActionsGrade 1
ICE score 7-9If 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 consciousnessNot attributable to any other cause.: awakens spontaneously.• Withhold ELREXFIO until ICANS resolves.See Table 2for recommendations on restarting ELREXFIO after dose delays.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.
Grade 2
ICE score 3-6
Or depressed level of consciousness: awakens to voice.• Withhold ELREXFIO until ICANS resolves.• Administer dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent medications.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 a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization.
Grade 3
(First occurrence)
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
• Withhold ELREXFIO until ICANS resolves.• Administer dexamethasone10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.• Patients should be hospitalized for 48 hours following the next dose of ELREXFIO.
Grade 3 (recurrent)
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
• Permanently discontinue ELREXFIO.• Administer dexamethasone10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.
Grade 4
ICE score 0
Or, depressed level of consciousnesseither:• 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 ELREXFIO.• Administer dexamethasone10 mg intravenously 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 for 3 days.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.
Table 5. Recommendations for Management of Neurologic Toxicity, Excluding ICANS Adverse ReactionSeverityActionsNeurologic Toxicity (excluding ICANS)
Grade 1
• Withhold ELREXFIO until neurologic toxicity symptoms resolve or stabilize.
Grade 2
Grade 3 (First occurrence)
• Withhold ELREXFIO until neurologic toxicity symptoms improve to Grade 1 or less.• Provide supportive therapy.
Grade 3 (Recurrent)
Grade 4
• Permanently discontinue ELREXFIO.• Provide supportive therapy, which may include intensive care.
Table 6. Recommended Dosage Modifications for Other Adverse Reactions Adverse ReactionsSeverityActionsHematologic Adverse Reactions
[see Warnings and Precautions (5.5)]Absolute neutrophil count less than 0.5 x 109/L
• Withhold ELREXFIO until absolute neutrophil count is 0.5 x 109/L or higher.See Table 2for recommendations on restarting ELREXFIO after dose delays.
Febrile neutropenia
• Withhold ELREXFIO until absolute neutrophil count is 1 x 109/L or higher and fever resolves.
Hemoglobin less than 8 g/dL
• Withhold ELREXFIO 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 ELREXFIO until platelet count is 25,000/mcL or higher and no evidence of bleeding.
Infections and Other Non-hematologic Adverse ReactionsBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.
[see Warnings and Precautions (5.4, 5.6)and Adverse Reactions (6.1)]Grade 3
• Withhold ELREXFIO until adverse reaction improves to ≤Grade 1 or baseline.
Grade 4
• Consider permanent discontinuation of ELREXFIO.• If ELREXFIO is not permanently discontinued, withhold subsequent treatment doses of ELREXFIO (e.g., doses administered after ELREXFIO step-up dosing schedule) until adverse reaction improves to Grade 1 or less.
]5.1 Cytokine Release Syndrome (CRS)ELREXFIO can cause CRS, including life-threatening or fatal reactions
[see Adverse Reactions (6.1)].In the clinical trial, CRS occurred in 58% of patients who received ELREXFIO at the recommended dosing schedule
[see Dosage and Administration (2.2)], with Grade 1 CRS in 44% of patients, Grade 2 CRS in 14% of patients, and Grade 3 CRS in 0.5% of patients. Recurrent CRS occurred in 13% of patients. Most patients experienced CRS after the first step-up dose (43%) or the second step-up dose (19%), with 7% of patients having CRS after the first treatment dose and 1.6% of patients after a subsequent dose. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose, with a median duration of 2 (range: 1 to 19) days.Clinical signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes.
Initiate therapy according to the ELREXFIO step-up dosing schedule to reduce risk of CRS and monitor patients following administration of ELREXFIO accordingly
[see Dosage and Administration (2.2, 2.5)]. Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS[see Dosage and Administration (2.3)].Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, evaluate patients immediately for hospitalization. Manage CRS according to the recommendations and consider further management per current practice guidelines. Withhold or permanently discontinue ELREXFIO based on severity
[see Dosage and Administration (2.5)].ELREXFIO is available only through a restricted program under a REMS
[see Warnings and Precautions (5.3)].• Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity[see2.5 Dosage Modifications for Adverse ReactionsDosage reductions of ELREXFIO are not recommended.
Dosage delays may be required to manage toxicities related to ELREXFIO
[see Warnings and Precautions (5)]. Recommendations on restarting ELREXFIO after a dose delay are provided in Table 2.See Table 3and Table 4for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table 5for recommended actions for neurologic toxicity excluding ICANS and Table 6for recommended actions for other adverse reactions following administration of ELREXFIO. Consider further management per current practice guidelines.
Management of CRS, Neurologic Toxicity Including ICANSCytokine 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 ELREXFIO until CRS resolves. Manage CRS 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 CRS GradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS.Presenting SymptomsActionsGrade 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 anti-cytokine therapy.
• Withhold ELREXFIO until CRS resolves.See Table 2for recommendations on restarting ELREXFIO after dose delays.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 2
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension responsive to fluid and not requiring vasopressors, and/or• Oxygen requirement of low-flow nasal cannulaLow-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.or blow-by
• Withhold ELREXFIO until CRS resolves.• Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 3
(First occurrence)
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension requiring one vasopressor with or without vasopressin, and/or• Oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask
• Withhold ELREXFIO until CRS resolves.• Provide supportive therapy, which may include intensive care.• Patients should be hospitalized for 48 hours following the next dose of ELREXFIO.• Administer pretreatment medications prior to next dose of ELREXFIO.
Grade 3 (Recurrent)
Temperature ≥100.4 °F (38 °C) with either:
• Hypotension requiring one vasopressor with or without vasopressin, and/or• Oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask
• Permanently discontinue therapy with ELREXFIO.• Provide supportive therapy, which may include intensive care.
Grade 4
Temperature ≥100.4 °F (38 °C) with either:
• 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 therapy with ELREXFIO.• Provide supportive therapy, which may include intensive care.
Neurologic Toxicity Including ICANSManagement recommendations for ICANS and neurologic toxicity are summarized in Table 4 and Table 5.
At the first sign of neurologic toxicity, including ICANS, withhold ELREXFIO 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 4 and consider further management per current practice guidelines.Table 4. Recommendations for Management of ICANS GradeBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS.Presenting SymptomsManagement is determined by the most severe event, not attributable to any other cause.ActionsGrade 1
ICE score 7-9If 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 consciousnessNot attributable to any other cause.: awakens spontaneously.• Withhold ELREXFIO until ICANS resolves.See Table 2for recommendations on restarting ELREXFIO after dose delays.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.
Grade 2
ICE score 3-6
Or depressed level of consciousness: awakens to voice.• Withhold ELREXFIO until ICANS resolves.• Administer dexamethasoneAll references to dexamethasone administration are dexamethasone or equivalent medications.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 a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization.
Grade 3
(First occurrence)
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
• Withhold ELREXFIO until ICANS resolves.• Administer dexamethasone10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.• Patients should be hospitalized for 48 hours following the next dose of ELREXFIO.
Grade 3 (recurrent)
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
• Permanently discontinue ELREXFIO.• Administer dexamethasone10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.
Grade 4
ICE score 0
Or, depressed level of consciousnesseither:• 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 ELREXFIO.• Administer dexamethasone10 mg intravenously 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 for 3 days.• Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management.• Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis.• Provide supportive therapy, which may include intensive care.
Table 5. Recommendations for Management of Neurologic Toxicity, Excluding ICANS Adverse ReactionSeverityActionsNeurologic Toxicity (excluding ICANS)
Grade 1
• Withhold ELREXFIO until neurologic toxicity symptoms resolve or stabilize.
Grade 2
Grade 3 (First occurrence)
• Withhold ELREXFIO until neurologic toxicity symptoms improve to Grade 1 or less.• Provide supportive therapy.
Grade 3 (Recurrent)
Grade 4
• Permanently discontinue ELREXFIO.• Provide supportive therapy, which may include intensive care.
Table 6. Recommended Dosage Modifications for Other Adverse Reactions Adverse ReactionsSeverityActionsHematologic Adverse Reactions
[see Warnings and Precautions (5.5)]Absolute neutrophil count less than 0.5 x 109/L
• Withhold ELREXFIO until absolute neutrophil count is 0.5 x 109/L or higher.See Table 2for recommendations on restarting ELREXFIO after dose delays.
Febrile neutropenia
• Withhold ELREXFIO until absolute neutrophil count is 1 x 109/L or higher and fever resolves.
Hemoglobin less than 8 g/dL
• Withhold ELREXFIO 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 ELREXFIO until platelet count is 25,000/mcL or higher and no evidence of bleeding.
Infections and Other Non-hematologic Adverse ReactionsBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.
[see Warnings and Precautions (5.4, 5.6)and Adverse Reactions (6.1)]Grade 3
• Withhold ELREXFIO until adverse reaction improves to ≤Grade 1 or baseline.
Grade 4
• Consider permanent discontinuation of ELREXFIO.• If ELREXFIO is not permanently discontinued, withhold subsequent treatment doses of ELREXFIO (e.g., doses administered after ELREXFIO step-up dosing schedule) until adverse reaction improves to Grade 1 or less.
,.]5.2 Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)ELREXFIO can cause serious or life-threatening neurologic toxicity, including ICANS
[see Adverse Reactions (6.1)].In the clinical trial, neurologic toxicity occurred in 59% of patients who received ELREXFIO at the recommended dosing schedule
[see Dosage and Administration (2.2)], with Grade 3 or 4 neurologic toxicity occurring in 7% of patients. Neurologic toxicities included headache (18%), encephalopathy (15%), motor dysfunction (13%), sensory neuropathy (13%), and Guillain-Barré Syndrome (0.5%).In the clinical trial, ICANS occurred in 3.3% of patients who received ELREXFIO at the recommended dosing schedule
[see Dosage and Administration (2.2)]. Most patients had ICANS after the first step-up dose (2.7%), 1 (0.5%) patient had ICANS after the second step-up dose and 1 (0.5%) patient had ICANS after subsequent dose(s). Recurrent ICANS occurred in 1.1% of patients. The median time to onset was 3 (range: 1 to 4) days after the most recent dose, with a median duration of 2 (range: 1 to 18) days. The most frequent clinical manifestations of ICANS included a depressed level of consciousness and Grade 1 or Grade 2 Immune Effector Cell-Associated Encephalopathy (ICE) scores. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity occur. Monitor patients for signs and symptoms of neurologic toxicities during treatment with ELREXFIO. At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity. Withhold or permanently discontinue ELREXFIO based on severity per recommendations
[see Dosage and Administration (2.5)]and consider further management per current practice guidelines.Due to the potential for neurologic toxicity including ICANS, patients receiving ELREXFIO are at risk of depressed level of consciousness. Advise patients not to drive or operate heavy or potentially dangerous machinery for 48 hours after completing each of the 2 step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve
[see Dosage and Administration (2.2)].ELREXFIO is available only through a restricted program under a REMS
[see Warnings and Precautions (5.3)].• Because of the risk of CRS and neurologic toxicity, including ICANS, ELREXFIO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ELREXFIO REMS[see.]5.3 ELREXFIO REMSELREXFIO is available only through a restricted program under a REMS called the ELREXFIO REMS because of the risks of CRS and neurologic toxicity, including ICANS
[see Warnings and Precautions (5.1, 5.2)].Notable requirements of the ELREXFIO REMS include the following:
• Prescribers must be certified with the program by enrolling and completing training.• Prescribers must counsel patients receiving ELREXFIO about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with ELREXFIO Patient Wallet Card.• Pharmacies and healthcare settings that dispense ELREXFIO must be certified with the ELREXFIO REMS program and must verify prescribers are certified through the ELREXFIO REMS program.• Wholesalers and distributers must only distribute ELREXFIO to certified pharmacies or healthcare settings.
Further information about the ELREXFIO REMS program is available at www.ELREXFIOREMS.comor by telephone at 1‑844‑923‑7845.
Dosage and Administration, Recommended Dosage ( For subcutaneous injection only. The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24. For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule. For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule. Continue treatment with ELREXFIO until disease progression or unacceptable toxicity. Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.3)] .
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Dosage and Administration, Restarting ELREXFIO After Dosage Delay ( If a dose of ELREXFIO is delayed, restart therapy based on the recommendations listed in Table 2 and resume the dosing schedule accordingly [see Dosage and Administration (2.2) ] . Administer pre-treatment medications as indicated in Table 2.
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Dosage and Administration, Preparation and Administration Instructions ( ELREXFIO is intended for subcutaneous use by a healthcare provider only. ELREXFIO should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)] .ELREXFIO 76 mg/1.9 mL (40 mg/mL) vial and 44 mg/1.1 mL (40 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration. ELREXFIO is a clear to slightly opalescent, and colorless to pale brown liquid solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer if solution is discolored or contains particulate matter. Use aseptic technique to prepare and administer ELREXFIO. Preparation ELREXFIO vials are for one-time use in a single patient and do not contain any preservatives. Prepare ELREXFIO following the instructions below (see Table 7) depending on the required dose.
Remove the appropriate strength ELREXFIO vial from refrigerated storage [2 °C to 8 °C (36 °F to 46 °F)]. Once removed from refrigerated storage, equilibrate ELREXFIO to ambient temperature [15 °C to 30 °C (59 °F to 86 °F)]. Do not warm ELREXFIO in any other way. Withdraw the required injection volume of ELREXFIO from the vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material. Discard unused portion. Administration Inject the required volume of ELREXFIO into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, ELREXFIO may be injected into the subcutaneous tissue at other sites (e.g., thigh). Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact. Storage of Prepared Syringe If the prepared dosing syringe is not used immediately, the syringemay be stored refrigerated between 2 °Cto 8 °C (36 °Fto 46 °F) for a maximum of 72 hours or between 8 °C to 25 °C (46 °F to 77 °F) for a maximum of24 hours. Once removed from refrigerated storage, the prepared syringe must be used or discarded. | 7/2025 | ||||||||||||||||||||||||||||||
ELREXFIO is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate and durability of response
The efficacy of ELREXFIO monotherapy was evaluated in patients with relapsed or refractory multiple myeloma in an open-label, single arm, multi-center study (MagnetisMM-3, NCT04649359). The study included patients who were refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. MagnetisMM-3 included 123 patients naïve to prior BCMA-directed therapy (pivotal Cohort A) and 64 patients with prior BCMA-directed antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) T-cell therapy (supportive Cohort B). Patients had measurable disease by International Myeloma Working Group (IMWG) criteria at enrollment. The study included patients with an Eastern Cooperative Oncology Group (ECOG) score of ≤2, adequate baseline bone marrow (absolute neutrophil count ≥1.0 x 109/L, platelet count ≥25 x 109/L, hemoglobin level ≥8 g/dL), renal (CrCL ≥ 30 mL/min), and hepatic (AST and ALT ≤2.5 x ULN, total bilirubin ≤2 x ULN) function, and left-ventricular ejection fraction ≥40%. Patients with a stem cell transplant within 12 weeks prior to enrollment and active infections were excluded from the study.
Eligible patients received subcutaneous administration of ELREXFIO at step-up doses of 12 mg on Day 1 and 32 mg on Day 4 of treatment, followed by the first treatment dose of ELREXFIO (76 mg) on Day 8 of treatment. Thereafter, patients received 76 mg once weekly. After 24 weeks, in patients who achieved an IMWG response category of partial response or better with responses persisting for at least 2 months, the dose interval was changed from every week to every 2 weeks.
The 123 patients enrolled in pivotal Cohort A had received a median of 5 prior lines of therapy (range: 2 to 22). Ninety-seven patients who were not exposed to prior BCMA-directed therapy and received at least four prior lines of therapy comprised the efficacy population. Among the 97 patients in the efficacy population, the median age was 69 (range: 46 to 89) years with 18.6% of patients ≥75 years of age. Forty percent were female; 59.8% were White, 13.4% were Asian, 7.2% were Hispanic/Latino, 5.2% were Black or African American. Disease stage (R-ISS) at study entry was 20.6% in Stage I, 53.6% in Stage II, and 17.5% in Stage III. The median time since initial diagnosis of multiple myeloma to enrollment was 79.6 (range: 16 to 228) months. 96.9% were triple-class refractory, and 94.8% were refractory to their last line of therapy. 69.1% received prior autologous stem cell transplantation, and 7.2% received prior allogenic stem cell transplantation. High-risk cytogenetics [t(4;14), t(14;16), or del(17p)] were present in 22.7% of patients. 34.0% of patients had extramedullary disease at baseline by BICR.
Efficacy was based on response rate and duration of response (DOR), as assessed by BICR based on IMWG criteria. Efficacy results from BCMA-directed therapy naïve patients are shown in Table 11.
The median (range) time to first response (TTR) was 1.22 (0.9 to 6.5) months. With a median follow-up of 11.1 months (95% CI: 10.6, 12.0) among responders, the DOR rate at 6 months was 90.4% (95% CI: 78.4%, 95.9%) and at 9 months was 82.3% (95% CI: 67.1%, 90.9%).
| Abbreviations: CI = Confidence interval; NR = Not reached; NE = Not estimable. | |
N = 97 | |
Objective Response Rate (ORR: sCR+CR+VGPR+PR), n (%) (95% CI) | 56 (57.7%) (47.3, 67.7) |
Complete response (CR) or betterComplete response or better = Stringent complete response (sCR) + complete response (CR). | 25 (25.8%) |
Very good partial response (VGPR) | 25 (25.8%) |
Partial response (PR) | 6 (6.2%) |
Duration of Response (DOR) (months) Median (95% CI) |
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Among the 64 patients enrolled in Cohort B who previously received a PI, an IMiD, an anti-CD38 monoclonal antibody, and a BCMA-directed therapy, 63 patients received at least four prior lines of therapy. Patients had received a median of 8 prior lines of therapy (range: 4 to 19); 73% and 32% received prior BCMA-directed ADC and CAR T-cell therapy, respectively.
Confirmed ORR by BICR was 33.3% (95% CI: 22.0, 46.3). After a median (95% CI) follow-up of 10.2 (9.9, 11) months among responders, median DOR was not reached (95% CI: NE, NE) and the DOR rate at 9 months was 84.3% (95% CI: 58.7, 94.7).
ELREXFIO Dosing Schedule ( For subcutaneous injection only. The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24. For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule. For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule. Continue treatment with ELREXFIO until disease progression or unacceptable toxicity. Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.3)] .
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Dosing Schedule | Day | ELREXFIO Dose | |||||||||||||||||||||||||||||||
Step-up Dosing Schedule | Day 1 | Step-up dose 1 | 12 mg | ||||||||||||||||||||||||||||||
Day 4 | Step-up dose 2 | 32 mg | |||||||||||||||||||||||||||||||
Day 8 | First treatment dose | 76 mg | |||||||||||||||||||||||||||||||
Weekly Dosing Schedule | One week after first treatment dose and weekly thereafter through week 24 | Subsequent treatment doses | 76 mg | ||||||||||||||||||||||||||||||
Biweekly (Every 2 Week) Dosing ScheduleResponders only week 25 onward. | Week 25 and every 2 weeks thereafter through week 48 | Subsequent treatment doses | 76 mg | ||||||||||||||||||||||||||||||
Every 4 Week Dosing ScheduleIn patients who have maintained the response following 24 weeks of treatment at the biweekly dosing schedule. | Week 49 and every 4 weeks thereafter | Subsequent treatment doses | 76 mg | ||||||||||||||||||||||||||||||
• Patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. ()2.1 Important Dosing InformationAdminister ELREXFIO subcutaneously according to the step-up dosing schedule to reduce the incidence and severity of cytokine release syndrome (CRS).
Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended
[see Dosage and Administration (2.2, 2.3)].ELREXFIO 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, 5.2)].Due to the risk of CRS, patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.
• For subcutaneous injection only. ()2.2 Recommended DosageFor subcutaneous injection only.
The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24.
For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule.
For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule.Continue treatment with ELREXFIO until disease progression or unacceptable toxicity.
Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended
[see Dosage and Administration (2.3)].Table 1. ELREXFIO Dosing Schedule Note: See Table 2for recommendations on restarting ELREXFIO after dose delays. Dosing ScheduleDayELREXFIO DoseStep-up Dosing Schedule
Day 1Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose
[see Dosage and Administration (2.3)].Step-up dose 1
12 mg
Day 4
A minimum of 2 days should be maintained between step-up dose 1 (12 mg) and step-up dose 2 (32 mg).Step-up dose 2
32 mg
Day 8
A minimum of 3 days should be maintained between step-up dose 2 (32 mg) and the first treatment (76 mg) dose.First treatment dose
76 mg
Weekly Dosing Schedule
One week after first treatment dose and weekly thereafterA minimum of 6 days should be maintained between treatment doses.through week 24
Subsequent treatment doses
76 mg
Biweekly (Every 2 Week) Dosing Schedule
*Responders only week 25 onwardWeek 25 and every 2 weeks thereafter
through week 48Subsequent treatment doses
76 mg
Every 4 Week Dosing Schedule*In patients who have maintained the response following 24 weeks of treatment at the biweekly dosing scheduleWeek 49 and every 4 weeks thereafterSubsequent treatment doses76 mg• Administer pre-treatment medications as recommended. ()2.3 Recommended Pre-treatment MedicationsAdminister the following pre-treatment medications approximately 1 hour before the first three doses of ELREXFIO in the step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described in Table 1 to reduce the risk of CRS
[see Warnings and Precautions (5.1)]:• acetaminophen (or equivalent) 650 mg orally• dexamethasone (or equivalent) 20 mg orally or intravenously• diphenhydramine (or equivalent) 25 mg orally
• See Full Prescribing Information for instructions on preparation and administration. ()2.6 Preparation and Administration InstructionsELREXFIO is intended for subcutaneous use by a healthcare provider only.
ELREXFIO should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and neurologic toxicity, including ICANS
[see Warnings and Precautions (5.1, 5.2)].ELREXFIO 76 mg/1.9 mL (40 mg/mL) vial and 44 mg/1.1 mL (40 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration.
ELREXFIO is a clear to slightly opalescent, and colorless to pale brown liquid solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer if solution is discolored or contains particulate matter.
Use aseptic technique to prepare and administer ELREXFIO.
PreparationELREXFIO vials are for one-time use in a single patient and do not contain any preservatives.
Prepare ELREXFIO following the instructions below (see Table 7) depending on the required dose.
Table 7. Injection Volumes Total Dose (mg)Volume of Injection12 mg
0.3 mL
32 mg
0.8 mL
76 mg
1.9 mL
Remove the appropriate strength ELREXFIO vial from refrigerated storage [2 °C to 8 °C (36 °F to 46 °F)]. Once removed from refrigerated storage, equilibrate ELREXFIO to ambient temperature [15 °C to 30 °C (59 °F to 86 °F)]. Do not warm ELREXFIO in any other way.
Withdraw the required injection volume of ELREXFIO from the vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material. Discard unused portion.
AdministrationInject the required volume of ELREXFIO into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, ELREXFIO may be injected into the subcutaneous tissue at other sites (e.g., thigh).
Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.
Storage of Prepared SyringeIf the prepared dosing syringe is not used immediately,
thesyringemay be stored refrigeratedbetween 2 °Cto 8 °C(36 °Fto 46 °F) for a maximum of 72 hours or between 8 °C to 25 °C (46 °F to 77°F) for a maximum of24 hours. Once removed from refrigerated storage, the prepared syringe must be used or discarded.
ELREXFIO injection is a clear to slightly opalescent, and colorless to pale brown liquid solution available as:
• 76 mg/1.9 mL (40 mg/mL) in a single-dose vial• 44 mg/1.1 mL (40 mg/mL) in a single-dose vial
There are no data on the presence of elranatamab-bcmm in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk.
Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ELREXFIO and for 4 months after the last dose.