Elrexfio Drug Information
Generic name: ELRANATAMAB-BCMM
Uses of Elrexfio
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. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s).
Dosage & Administration of Elrexfio
Important Dosing Information Administer
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. 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.
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.
Recommended Dosage
For subcutaneous injection only. The recommended dosing schedule for ELREXFIO is provided in Table 1. For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule.
Continue treatment with ELREXFIO until disease progression or unacceptable toxicity. Table 1.
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. Administer pre-treatment medications as indicated in Table 2. Table 2.
Recommendation for Restarting Therapy with ELREXFIO After Dosage Delay. If tolerated, increase to Dosage reductions of ELREXFIO are not recommended. Dosage delays may be required to manage toxicities related to ELREXFIO.
Recommendations on restarting ELREXFIO after a dose delay are provided in Table 2. See Table 3 and Table 4 for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table 5 for recommended actions for neurologic toxicity excluding ICANS and Table 6 for recommended actions for other adverse reactions following administration of ELREXFIO.
Consider further management per current practice guidelines. Management of CRS, Neurologic Toxicity Including ICANS Cytokine Release Syndrome (CRS) Management recommendations for CRS are summarized in Table 3. Identify CRS based on clinical presentation.
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 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, bilevel positive airway pressure, intubation, and mechanical ventilation) • Permanently discontinue therapy with ELREXFIO. • Provide supportive therapy, which may include intensive care. Neurologic Toxicity Including ICANS Management 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. Manage ICANS according to the recommendations in Table 4 and consider further management per current practice guidelines.
Table 4. Recommendations for Management of ICANS Table 5. Recommendations for Management of Neurologic Toxicity, Excluding ICANS Table 6.
Recommended Dosage Modifications for Other Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.
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. 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. Table 7.
Injection Volumes Total Dose (mg) Volume of Injection mL Remove the appropriate strength ELREXFIO vial from refrigerated storage. Once removed from refrigerated storage, equilibrate ELREXFIO to ambient temperature. 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. Once removed from refrigerated storage, the prepared syringe must be used or discarded.
| ELREXFIO Dosing Schedule ( 2.2 ) | |||
| 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 Schedule Responders only week 25 onward. | Week 25 and every 2 weeks thereafter through week 48 | Subsequent 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 schedule. | Week 49 and every 4 weeks thereafter | Subsequent treatment doses | 76 mg |
| Note: See Table 2 for recommendations on restarting ELREXFIO after dose delays. | |||
| Dosing Schedule | Day | ELREXFIO Dose | |
| Step-up Dosing Schedule | Day 1 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 [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 thereafter A 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 onward | Week 25 and every 2 weeks thereafter through week 48 | Subsequent 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 schedule | Week 49 and every 4 weeks thereafter | Subsequent treatment doses | 76 mg |
| Last Dose Administered | Time Since the Last Dose Administered | Action for Next Dose |
|---|---|---|
| Step-up dose 1 (12 mg) | 2 weeks or less (≤14 days) | Restart ELREXFIO at step-up dose 2 (32 mg). Administer pre-treatment medications prior to the ELREXFIO dose [see Dosage and Administration (2.3) ]. If tolerated, increase to 76 mg 4 days later. |
| Greater than 2 weeks (>14 days) | Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). | |
| Step-up dose 2 (32 mg) | 2 weeks or less (≤14 days) | Restart ELREXFIO at 76 mg. |
| Greater than 2 weeks to less than or equal to 4 weeks (15 days to ≤28 days) | Restart ELREXFIO at step-up dose 2 (32 mg). If tolerated, increase to 76 mg 1 week later. | |
| Greater than 4 weeks (>28 days) | Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). | |
| Any weekly treatment dose (76 mg) | 8 weeks or less (≤ 56 days) | Restart ELREXFIO at 76 mg. |
| Greater than 8 weeks to less or equal to 12 weeks (57 days to ≤84 days) Consider benefit-risk of restarting ELREXFIO in patients who require a dose delay of more than 56 days due to an adverse reaction. | Restart ELREXFIO at step-up dose 2 (32 mg). If tolerated, increase to 76 mg 1 week later. | |
| Greater than 12 weeks (>84 days) | Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). | |
| Any biweekly or every-4-week treatment dose (76 mg) | 12 weeks or less (≤84 days) | Restart ELREXFIO at 76 mg. |
| Greater than 12 weeks (>84 days) | Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). |
| Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria 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 anti-cytokine therapy. | • Withhold ELREXFIO until CRS resolves. See Table 2 for 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 cannula Low-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. |
| Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS. | Presenting Symptoms Management is determined by the most severe event, 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 ELREXFIO until ICANS resolves. See Table 2 for 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 dexamethasone All 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 dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Monitor neurologic symptoms and consider consultation with 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 dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Monitor neurologic symptoms and consider consultation with 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 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 ELREXFIO. • Administer dexamethasone 10 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. |
| Adverse Reaction | Severity | Actions |
|---|---|---|
| Neurologic 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. |
| Adverse Reactions | Severity | Actions |
|---|---|---|
| Hematologic Adverse Reactions [see Warnings and Precautions (5.5) ] | Absolute neutrophil count less than 0.5 x 10 9 /L | • Withhold ELREXFIO until absolute neutrophil count is 0.5 x 10 9 /L or higher. See Table 2 for recommendations on restarting ELREXFIO after dose delays. |
| Febrile neutropenia | • Withhold ELREXFIO until absolute neutrophil count is 1 x 10 9 /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 Reactions Based 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. |
| Total Dose (mg) | Volume of Injection |
|---|---|
| 12 mg | 0.3 mL |
| 32 mg | 0.8 mL |
| 76 mg | 1.9 mL |
Side Effects of Elrexfio
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 MagnetisMM-3 The safety of ELREXFIO was evaluated in MagnetisMM-3. Among patients who received ELREXFIO, 42% were exposed for 6 months or longer and 9% were exposed for one year or longer.
Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis ( %), acute respiratory distress syndrome ( %). Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients.
Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%). Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.
The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. Table 8 summarizes adverse reactions in MagnetisMM-3.
Table 8. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barré syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy. Table 9 summarizes laboratory abnormalities in MagnetisMM-3.
Table 9. Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Laboratory tests were graded according to NCI-CTCAE Version 5.0.
| Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria. | ||
| System Organ Class Preferred Term | ELREXFIO N = 183 | |
| All Grades (%) | Grade 3 or 4 (%) | |
| Immune system disorders | ||
| Cytokine release syndrome | 58 | 0.5 Only grade 3 adverse reactions occurred. |
| Hypogammaglobulinemia Includes other related terms. | 13 | 2.2 |
| General disorders and site administration conditions | ||
| Fatigue | 43 | 6 |
| Injection site reaction | 37 | 0 |
| Pyrexia | 21 | 2.7 |
| Edema | 18 | 1.1 |
| Gastrointestinal disorders | ||
| Diarrhea | 36 | 1.1 |
| Nausea | 21 | 0 |
| Constipation | 14 | 0 |
| Vomiting | 14 | 0 |
| Infections | ||
| Upper respiratory tract infection | 36 | 4.9 |
| Pneumonia Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. | 32 | 19 |
| Sepsis Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. | 15 | 11 |
| Urinary tract infection | 12 | 4.4 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain | 34 | 2.7 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 26 | 1.1 |
| Skin and Subcutaneous Tissue disorders | ||
| Rash Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. | 26 | 0 |
| Dry skin | 14 | 0 |
| Skin exfoliation | 10 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 24 | 0 |
| Dyspnea | 15 | 3.3 |
| Nervous system disorders | ||
| Headache | 18 | 0 |
| Encephalopathy Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. | 14 | 2.2 |
| Sensory neuropathy Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. | 13 | 0.5 |
| Motor dysfunction Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. | 14 | 1.1 |
| Cardiac disorders | ||
| Cardiac arrhythmia | 16 | 1.6 |
| Vascular disorders | ||
| Hemorrhage | 13 | 1.6 |
| Psychiatric disorders | ||
| Insomnia | 13 | 0 |
| Injury, poisoning and procedural complications | ||
| Fall | 10 | 0.5 |
| Laboratory Abnormality | ELREXFIO The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value. | |
|---|---|---|
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||
| Lymphocyte count decreased | 91 | 84 |
| White blood cell decreased | 69 | 40 |
| Hemoglobin decreased | 68 | 43 |
| Neutrophil count decreased | 62 | 51 |
| Platelet count decreased | 61 | 32 |
| Chemistry | ||
| Albumin decreased | 55 | 6 |
| AST increase | 40 | 6 |
| Creatinine increased | 38 | 3.3 |
| Potassium decreased | 36 | 8 |
| ALT increase | 36 | 3.8 |
| Alkaline phosphatase increased | 34 | 1.1 |
| Creatinine clearance decreased | 32 | 10 |
Warnings & Cautions for Elrexfio
Cytokine Release Syndrome (CRS) ELREXFIO can cause
CRS, including life-threatening or fatal reactions. 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.
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. Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS.
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. ELREXFIO is available only through a restricted program under a REMS.
Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) ELREXFIO can cause serious or life-threatening neurologic toxicity, including ICANS. In the clinical trial, ICANS occurred in 3.3% of patients who received ELREXFIO at the recommended dosing schedule. Recurrent ICANS occurred in 1.1% of patients.
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. 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. 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.
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.com or by telephone at 1‑844‑923‑7845.
Infections ELREXFIO can cause severe, life-threatening, or fatal infections. The most common serious infections reported (≥5%) were pneumonia and sepsis. Do not initiate treatment with ELREXFIO in patients with active infections.
Monitor patients for signs and symptoms of infection prior to and during treatment with ELREXFIO and treat appropriately. Administer prophylactic antimicrobial and anti-viral medications according to current practice guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate.
Neutropenia ELREXFIO can cause neutropenia and febrile neutropenia. Febrile neutropenia occurred in 2.2% of patients. Monitor complete blood cell counts at baseline and periodically during treatment.
Provide supportive care according to current practice guidelines. Monitor patients with neutropenia for signs of infection. Withhold ELREXFIO based on severity.
Hepatotoxicity ELREXFIO can cause hepatotoxicity. Grade 3 or 4 total bilirubin elevations occurred in 0.5% of patients. Liver enzyme elevation can occur with or without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold ELREXFIO or consider permanent discontinuation of ELREXFIO based on severity.
Embryo-Fetal Toxicity Based on its mechanism of action, ELREXFIO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ELREXFIO and for 4 months after the last dose.
Drug Interactions with Elrexfio
For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with ELREXFIO. ELREXFIO causes release of cytokines that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates.
Increased exposure of CYP substrates is more likely to occur after the first dose of ELREXFIO Day 1 and up to 14 days after the 32 mg dose on Day 4 and during and after CRS.
Pregnancy Safety for Elrexfio
Pregnancy Risk Summary Based on the mechanism of action, ELREXFIO may cause fetal harm when administered to a pregnant woman. There are no available data on the use of ELREXFIO in pregnant women to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with ELREXFIO.
Elranatamab-bcmm causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on the finding of B-cell depletion in non-pregnant animals, elranatamab-bcmm can cause B-cell lymphocytopenia in infants exposed to elranatamab-bcmm in-utero. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, elranatamab-bcmm has the potential to be transmitted from the mother to the developing fetus.
Advise women of the potential risk to the fetus. ELREXFIO is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with ELREXFIO should be considered. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.
Pediatric Use of Elrexfio
Pediatric Use The safety and effectiveness of ELREXFIO in pediatric patients have not been established.
Clinical Studies of Elrexfio
Relapsed or Refractory Multiple Myeloma
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. Patients with a stem cell transplant within 12 weeks prior to enrollment and active infections were excluded from the study. 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. 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. Disease stage (R-ISS) at study entry was 20.6% in Stage I, 53.6% in Stage II, and 17.5% in Stage III.
High-risk cytogenetics 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. Table 11. Efficacy Results from BCMA-directed Therapy Naïve Patients 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: received prior BCMA-directed ADC and CAR T-cell therapy, respectively. Confirmed ORR by BICR was
| 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 better Complete 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) | NR (12.0, NE) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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