Elranatamab: Drug information

(For additional information see "Elranatamab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Cytokine release syndrome

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving elranatamab. Initiate treatment with elranatamab step-up dosing schedule to reduce the risk of CRS. Withhold elranatamab until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving elranatamab. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold elranatamab until the neurologic toxicity resolves or permanently discontinue based on severity.

Risk Evaluation and Mitigation Strategy

Because of the risk of CRS and neurologic toxicity, including ICANS, elranatamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ELREXFIO REMS.

Brand Names: US

Elrexfio

Pharmacologic Category

Antineoplastic Agent, Anti-BCMA;
Antineoplastic Agent, Anti-CD3;
Antineoplastic Agent, Bispecific T Cell Engager;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Note: Due to the risk of cytokine release syndrome (CRS), patients should be hospitalized for 48 hours after elranatamab step-up dose 1, and for 24 hours after elranatamab step-up dose 2.

Premedication: Premedicate ~1 hour prior to all doses within the elranatamab step-up dosing schedule to reduce the risk and severity of CRS. Premedication may be necessary prior to subsequent doses in patients who repeat doses within the elranatamab step-up dosing schedule (following a dose delay), or who experienced CRS following the prior elranatamab dose.

Premedication should include a corticosteroid (IV or oral dexamethasone 20 mg or equivalent), a histamine H₁ antagonist (oral diphenhydramine 25 mg or equivalent), and antipyretics (oral acetaminophen 650 mg or equivalent).

Prophylaxis: Administer prophylactic antimicrobial and antiviral medications according to clinical practice guidelines. Note: In a clinical study, most patients received antiviral prophylaxis and nearly one-half of patients received prophylaxis against Pneumocystis jirovecii (Ref).

Multiple myeloma, relapsed or refractory

Multiple myeloma, relapsed or refractory:

Day 1 (step-up dose 1): SUBQ: 12 mg once.

Day 4 (step-up dose 2): SUBQ: 32 mg once. Note: A minimum of 2 days should be maintained between step-up dose 1 and step-up dose 2.

Day 8 (first treatment dose): SUBQ: 76 mg once. Note: A minimum of 3 days should be maintained between step-up dose 2 and the first treatment dose.

Weekly dosing schedule: SUBQ: 76 mg once weekly through week 24, starting 1 week after the first treatment dose. Note: A minimum of 6 days should be maintained between treatment doses.

Biweekly (every 2 weeks) dosing schedule (only in patients achieving a partial response or better at 24 weeks with response maintained for ≥2 months): SUBQ: 76 mg once every 2 weeks, starting week 25 and continuing every 2 weeks thereafter until disease progression or unacceptable toxicity (Ref). Note: A minimum of 6 days should be maintained between treatment doses.

**Recommendations** **for Restarting Elranatamab^a After Dose Delay**
Last elranatamab dose administered	Duration of delay from the last elranatamab dose administered	Action
^a Administer premedication prior to elranatamab administration and monitor accordingly. Due to the risk of cytokine release syndrome (CRS), patients should be hospitalized for 48 hours after elranatamab step-up dose 1, and for 24 hours after elranatamab step-up dose 2.
SUBQ: 12 mg (step-up dose 1)	≤14 days	Restart elranatamab step-up dosing schedule at step-up dose 2 (32 mg).^a If tolerated, resume step-up dosing increase to treatment dose (76 mg) 4 days later.
SUBQ: 12 mg (step-up dose 1)	>14 days	Restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg).^a
SUBQ: 32 mg (step-up dose 2)	≤14 days	Restart elranatamab at treatment dose (76 mg).^a
	>14 days to ≤28 days	Restart elranatamab step-up dosing schedule at step-up dose 2 (32 mg).^a If tolerated, resume step-up dosing increase to treatment dose (76 mg) 1 week later.
	>28 days	Restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg).^a
SUBQ: 76 mg (treatment dose)	≤42 days	Restart elranatamab at treatment dose (76 mg).
	>42 days to ≤84 days	Consider risk vs benefit of restarting elranatamab. Restart elranatamab step-up dosing schedule at step-up dose 2 (32 mg).^a If tolerated, resume step-up dosing increase to treatment dose (76 mg) 1 week later.
	>84 days	Consider risk vs benefit of restarting elranatamab. Restart elranatamab step-up dosing schedule at step-up dose 1 (12 mg).^a

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the MDRD equation.

eGFR ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in elranatamab pharmacokinetics were observed based on an eGFR 30 to 89 mL/minute.

eGFR 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

eGFR <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild impairment (total bilirubin ≥1 to 1.5 times ULN or any AST > ULN): There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in elranatamab pharmacokinetics was observed based on mild hepatic impairment.

Moderate to severe impairment (total bilirubin >1.5 times ULN with any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

Elranatamab dose reductions are not recommended for adverse reactions; however, dose delays may be necessary to manage toxicities. Refer to “Dosing: Adult” for recommendations on restarting elranatamab after dose delays.

Cytokine release syndrome: If cytokine release syndrome (CRS) is suspected, interrupt elranatamab until resolved; manage according to the table below and per clinical practice guidelines. Supportive therapy for CRS may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Evaluate and treat other causes of fever, hypoxia, and hypotension.

**Elranatamab-Related Cytokine Release Syndrome Management**
CRS grade^a	Symptoms	Actions
^a Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS.
^b Fever may be masked by antipyretics or anticytokine therapy.
^c CPAP = continuous positive airway pressure; BiPAP = bilevel positive airway pressure.
Grade 1	Temperature ≥38°C (100.4°F)^battributed to CRS.	Withhold elranatamab until CRS resolves. Administer premedication prior to the next elranatamab dose.
Grade 2	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension responsive to fluids and not requiring vasopressors and/or oxygen requirement of low-flow nasal cannula (≤6 L/minute) or blow-by.	Withhold elranatamab until CRS resolves. Administer premedication prior to the next elranatamab dose. Monitor for 48 hours following the next dose of elranatamab (ensure patient within proximity of healthcare facility or consider hospitalization).
Grade 3	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension requiring one vasopressor with or without vasopressin and/or oxygen requirement of high-flow nasal cannula (>6 L/minute), face mask, nonrebreather mask, or Venturi mask.	First occurrence: Withhold elranatamab until CRS resolves. Provide supportive therapy as clinically necessary (may include intensive care). Administer premedication prior to the next elranatamab dose. Patients should be hospitalized for 48 hours following the next elranatamab dose.
Grade 3		Recurrent grade 3 CRS: Permanently discontinue elranatamab. Provide supportive care as clinically necessary (may include intensive care).
Grade 4	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension requiring multiple vasopressors (excluding vasopressin) and/or oxygen requirement of positive pressure (eg, CPAP, BiPAP, intubation, and mechanical ventilation).^c	Permanently discontinue elranatamab. Provide supportive care as clinically necessary (may include intensive care).

Neurologic toxicity: Interrupt elranatamab at the first sign of neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and consider neurology evaluation. Rule out other causes of neurologic signs/symptoms. Supportive therapy may include intensive care for severe or life-threatening neurologic toxicities. Manage according to the table below and per clinical practice guidelines.

**Elranatamab-Related Neurologic Toxicity Management**
Adverse reaction	Severity	Actions
^aBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
^bManagement if determined by the most severe event (not attributable to any other cause).
^cIf patient is arousable and able to perform immune effector cell-associated encephalopathy (ICE) assessment: Orientation (oriented to year, month, city, hospital = 4 points) Naming (name 3 objects, eg, point to clock, pen, button = 3 points) Following commands (eg, “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point) Writing (ability to write a standard sentence = 1 point) Attention (count backwards from 100 by 10 = 1 point) If unarousable and unable to perform ICE assessment (Grade 4 ICANS = 0 points)
^d Not attributable to any other cause.
Neurologic toxicity (excluding ICANS)	Grade 1	Withhold elranatamab until neurologic toxicities/symptoms resolve or stabilize.
	Grade 2 or grade 3 (first occurrence)	Withhold elranatamab until neurologic toxicities/symptoms improve to ≤ grade 1. Provide supportive therapy as clinically appropriate.
	Recurrent grade 3 or grade 4	Permanently discontinue elranatamab. Provide supportive care as clinically appropriate (may include intensive care).
Recommendations for management of elranatamab-related ICANS
ICANS grade^a	Presenting symptoms^b	Actions
Grade 1	ICE score 7 to 9^c, or depressed level of consciousness^d(awakens spontaneously)	Withhold elranatamab until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (eg, consider initiating seizure prophylaxis with nonsedating, antiseizure medication).
Grade 2	ICE score 3 to 6^c, or depressed level of consciousness^d (awakens to voice)	Withhold elranatamab until ICANS resolves. Administer dexamethasone (or equivalent) 10 mg IV every 6 hours; continue dexamethasone until resolution to ≤ grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (eg, consider initiating seizure prophylaxis with nonsedating, antiseizure medication). Monitor for 48 hours following the next dose of elranatamab (ensure patient within proximity of healthcare facility or consider hospitalization).
Grade 3	ICE score 0 to 2^c, or depressed level of consciousness^d (awakens only to tactile stimulus), or seizures^d (either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention), or raised intracranial pressure (focal/local edema on neuroimaging^d)	First occurrence of grade 3 ICANS: Manage as per grade 2 ICANS. Provide supportive therapy as clinically appropriate (may include intensive care). Patients should be hospitalized for 48 hours following the next elranatamab dose.
Grade 3		Recurrent grade 3 ICANS: Permanently discontinue elranatamab. Manage as per grade 2 ICANS. Provide supportive therapy as clinically appropriate (may include intensive care).
Grade 4	ICE score 0^c, or depressed level of consciousness^d (either unarousable or requires vigorous/repetitive tactile stimuli to arouse, or stupor or coma), or seizures^d (either life-threatening prolonged seizure >5 minutes, or repetitive clinical or electrical seizures without return to baseline in between), or motor findings^d (deep focal motor weakness such as hemiparesis or paraparesis), or raised intracranial pressure/cerebral edema^d, with signs/symptoms including diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing triad	Permanently discontinue elranatamab. Manage as per grade 2 ICANS. Alternatively, instead of dexamethasone, consider methylprednisolone 1,000 mg IV daily for 3 days. Provide supportive therapy as clinically appropriate (may include intensive care).

**Recommended Elranatamab Dosage Modifications for Other Adverse Reactions**
Adverse reaction	Severity	Actions
Hematologic toxicity	ANC <500/mm³	Withhold elranatamab until ANC is ≥500/mm³.
	Febrile neutropenia	Withhold elranatamab until ANC is ≥1,000/mm³ and fever resolves.
	Hemoglobin <8 g/dL	Withhold elranatamab until hemoglobin is ≥8 g/dL.
	Platelets <25,000/mm³ or platelets 25,000 to 50,000/mm³ with bleeding	Withhold elranatamab until platelets are ≥25,000/mm³ and no evidence of bleeding.
Infections	All grades	Withhold elranatamab for active infection during the step-up dosing schedule. Consider treatment with SUBQ or IV immunoglobulin as appropriate.
	Grade 3	Withhold elranatamab until infection improves to ≤ grade 1.
	Grade 4	Consider permanent discontinuation of elranatamab. If not permanently discontinued, withhold subsequent treatment doses until infection improves to ≤ grade 1.
Other nonhematologic adverse reactions	Grade 3	Withhold elranatamab until adverse reaction improves to ≤ grade 1.
Other nonhematologic adverse reactions	Grade 4	Consider permanent discontinuation of elranatamab. If not permanently discontinued, withhold subsequent treatment doses until adverse reaction improves to ≤ grade 1

Dosing: Older Adult

Refer to adult dosing.

In a clinical study of elranatamab in patients with relapsed or refractory multiple myeloma, 62% of patients were ≥65 years of age, and 19% were ≥75 years of age.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Cardiovascular: Cardiac arrhythmia (16%), edema (18%)

Dermatologic: Skin rash (25%; including palmar-plantar erythrodysesthesia), xeroderma (13%)

Endocrine & metabolic: Decreased serum albumin (55%), decreased serum potassium (36%)

Gastrointestinal: Constipation (15%), decreased appetite (26%), diarrhea (36%; grade 3: 1%), nausea (22%), vomiting (14%)

Genitourinary: Urinary tract infection (12%)

Hematologic & oncologic: Decreased hemoglobin (68%; grades 3/4: 43%), decreased platelet count (61%; grades 3/4: 32%), decreased neutrophils (62%; grades 3/4: 51%), decreased white blood cell count (69%; grades 3/4: 40%), hemorrhage (13%; grades 3/4: 2%), hypogammaglobulinemia (13%; grade 3: 2%), lymphocytopenia (91%; grades 3/4: 84%)

Hepatic: Increased serum alanine aminotransferase (36%), increased serum alkaline phosphatase (34%), increased serum aspartate aminotransferase (40%)

Hypersensitivity: Cytokine release syndrome (13% to 58%)

Infection: Severe infection (42%; including opportunistic infection and sepsis [13% to 15%])

Local: Injection-site reaction (37%)

Nervous system: Fatigue (43%), headache (18%), insomnia (13%), neurotoxicity (59%; including encephalopathy [15%; serious: 3%], Guillain-Barré syndrome [<1%], immune effector cell-associated neurotoxicity syndrome [ICANS: 3%], motor dysfunction [13%], and peripheral sensory neuropathy [13%])

Neuromuscular & skeletal: Musculoskeletal pain (34%)

Renal: Decreased creatinine clearance (32%), increased serum creatinine (38%)

Respiratory: Cough (24%), dyspnea (15%), pneumonia (25% to 32%), upper respiratory tract infection (34%)

Miscellaneous: Fever (21%)

1% to 10%:

Cardiovascular: Heart failure (<10%), thrombosis (<10%)

Dermatologic: Exfoliation of skin (10%)

Gastrointestinal: Abdominal pain (<10%)

Hematologic & oncologic: Febrile neutropenia (2%)

Nervous system: Falling (10%)

Renal: Acute kidney injury (4%)

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Cytokine release syndrome: Cytokine release syndrome (CRS), including fatal or life-threatening reactions, may occur with elranatamab therapy; over half of CRS events were grades 1 or 2. Recurrent CRS has also been reported in 13% of patients. Most patients experienced CRS during the step-up doses or with the first treatment dose. A small percentage of patients experienced CRS with subsequent elranatamab doses. The median time to onset of CRS was 2 days (range: 1 to 9 days) after the most recent dose and the median duration was 2 days (range: 1 to 19 days). Clinical signs/symptoms of CRS include (but are not limited to) fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated transaminases. At the first sign of CRS, immediately evaluate patients for hospitalization.

• Hematologic toxicity: Elranatamab may cause neutropenia and febrile neutropenia, including grade 3 or 4 neutropenia in ~50% of patients; febrile neutropenia occurred in a small percentage of patents.

• Hepatotoxicity: Hepatotoxicity may occur with elranatamab. Elevated AST and ALT occurred in over one-third of patients, including grade 3 or 4 elevations; total bilirubin elevations (including grade 3 or 4 events in 0.5% of patients) were also reported. Liver enzyme elevation may occur with or without concurrent CRS.

• Infection: Elranatamab may cause severe, life-threatening, or fatal infections. Serious infections (including opportunistic infections) occurred in 42% of patients, with grade 3 or 4 infections in approximately one-third of patients; fatal infections were reported in 7% of patients. The most common serious infections in treated patients were pneumonia and sepsis.

• Neurologic toxicity: Elranatamab may cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). In a clinical trial, neurologic toxicity occurred in over 50% of patients, with grade 3 or 4 events occurring in some patients. The most common neurologic events were headache, encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barré Syndrome. ICANS was observed in ~3.3% of patients, including recurrent events in some; most patients experienced ICANS within the step-up dosing schedule. The median time to onset of ICANS was 3 days (range: 1 to 4 days) after the most recent treatment dose with a median duration of 2 days (range: 1 to 18 days). ICANS may occur with or without the presence of CRS and may occur concurrently with CRS or after the resolution of CRS. Clinical manifestations of ICANS may include (but are not limited to) depressed level of consciousness and declining Immune Effector Cell-Associated Encephalopathy (ICE) scores. Patients are at risk of depressed level of consciousness; advise patients to not drive or operate heavy machinery during and for 48 hours after completion of the step-up dosing schedule and with new onset of any neurologic toxicity symptoms until resolution.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• REMS program: Elranatamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ELREXFIO REMS Program. Further information is available at http://www.ELREXFIOREMS.com or 1-844-923-7845.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Elrexfio: Elranatamab-bcmm 44 mg/1.1 mL (1.1 mL); Elranatamab-bcmm 76 mg/1.9 mL (1.9 mL) [contains edetate (edta) disodium, polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (Elrexfio Subcutaneous)

44MG/1.1ML (per mL): $8,242.56

76MG/1.9ML (per mL): $8,242.56

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

SUBQ: For SUBQ administration only. If refrigerated, allow solution to come to room temperature before administration. Administer SUBQ into the abdomen (preferred injection site); may be administered at other sites (eg, thigh). Do not inject into tattoos, scars, or areas where the skin is red, bruised, tender, hard, or not intact.

Administer in a facility with adequate medical personnel and appropriate equipment to manage severe adverse reactions.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Elrexfio: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf#page=22

Use: Labeled Indications

Multiple myeloma, relapsed or refractory: Treatment of relapsed or refractory multiple myeloma in adults who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Medication Safety Issues

High alert medication

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Elranatamab may increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status prior to treatment initiation.

Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last dose of elranatamab.

Pregnancy Considerations

Elranatamab is a bispecific humanized monoclonal antibody (IgG₂) that may cross the placenta. Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to elranatamab may cause fetal harm. Pregnancy may be compromised due to activation of the maternal immune system. In addition, newborns exposed to in utero may develop hypogammaglobulinemia; consider monitoring newborn immunoglobulin level.

Breastfeeding Considerations

It is not known if elranatamab is present in breast milk.

Elranatamab is a bispecific humanized monoclonal antibody (IgG₂). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 4 months after the last dose of elranatamab.

Monitoring Parameters

Monitor blood counts, liver enzymes, and bilirubin at baseline and during therapy as clinically indicated. Verify pregnancy status prior to treatment (in patients who could become pregnant).

Due to the risk of cytokine release syndrome (CRS), patients should be hospitalized for 48 hours after elranatamab step-up dose 1, and for 24 hours after elranatamab step-up dose 2. Monitor for CRS (signs/symptoms of CRS may include fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated transaminases) and signs/symptoms of neurologic toxicity. Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Monitor for signs/symptoms of infection prior to and during treatment, particularly in patients with neutropenia.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Elranatamab is a bispecific, humanized, IgG₂-alanine kappa, B-cell maturation antigen (BCMA)-directed T-cell engaging antibody that binds BCMA (present on plasma cells, plasmablasts, and multiple myeloma cells) and CD3 (present on T cells). Upon binding to both BCMA and CD3, lysis of BCMA-expressing malignant plasma cells by elranatamab occurs via T-cell activation and the release of proinflammatory cytokines (Lesokhin 2023).

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 7.76 L.

Metabolism: Into small peptides via catabolic pathways.

Bioavailability: SUBQ: 56.2%.

Half-life elimination: 22 days (at 76 mg dose level).

Time to peak: 7 days (range: 3 to 7 days).

Excretion: Clearance: 0.324 L/day after 24 weeks of dosing.

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Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]
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Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
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Topic 142431 Version 16.0

خرید پکیج

Elranatamab: Drug information