Teclistamab (Monograph)

Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for teclistamab-cqyv to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of teclistamab-cqyv and consists of the following: communication plan, elements to assure safe use, and implementation system. See the FDA REMS page [Web]

Warning

Risk of life-threatening or fatal CRS.
Reduce risk by using step-up dosing schedule.
If CRS develops, withdraw treatment until CRS resolves; may need to permanently discontinue depending on severity.

Risk of serious or life-threatening neurotoxicity, including ICANS.
Monitor for signs or symptoms of neurotoxicity.
If neurotoxicity develops, withdraw treatment until resolution; may need to permanently discontinue depending on severity.

Available only through a REMS restricted distribution program.

Introduction

Antineoplastic agent; bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.

Uses for Teclistamab

Multiple Myeloma

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

Designated an orphan drug by FDA for use in multiple myeloma.

Accelerated approval based on response rate. Continued approval may be contingent on verification of clinical benefit in confirmatory trials.

National Comprehensive Cancer Network (NCCN) recommends teclistamab-cqyv as one of several preferred options for patients with relapsed/refractory multiple myeloma after at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug.

Teclistamab Dosage and Administration

General

Pretreatment Screening

Assess liver enzyme and serum bilirubin concentrations prior to first dose.
Patients must enroll in REMS program and receive counseling on risks associated with cytokine release syndrome (CRS) and neurologic toxicity (including immune effector cell-associated neurotoxicity syndrome [ICANS]).
Assess for signs or symptoms of infection before initiating therapy; administer prophylactic antimicrobials according to guideline recommendations.
Assess complete blood cell (CBC) count at baseline.
Verify pregnancy status of females of reproductive potential.

Patient Monitoring

Patients should be hospitalized and monitored for CRS and neurotoxicity (including ICANS) for 48 hours after administration of each of the first 3 doses (i.e., step-up dosing schedule) of teclistamab. Hospitalization for 48 hours is also required for the next dose following some adverse reactions (e.g., CRS or ICANS Grade 2 or worse) and if doses within the step-up dosing schedule are repeated due to treatment delays.
Monitor for signs or symptoms of neurotoxicity, including ICANS, during treatment.
Monitor liver enzyme and serum bilirubin concentrations as clinically indicated during treatment.
Monitor for signs and symptoms of infection during treatment, and treat infections according to standards of care.
Monitor immunoglobulin concentrations during treatment and treat abnormalities according to guidelines.
Monitor CBC for neutropenia periodically during treatment and provide supportive care if neutropenia develops.
In patients with suspected CRS, consider laboratory monitoring for disseminated intravascular coagulation, hematology parameters, and pulmonary, cardiac, renal, and hepatic function.

Premedication and Prophylaxis

To reduce the risk of CRS and other adverse reactions, patients should be premedicated with dexamethasone 16 mg IV or oral (or an equivalent corticosteroid), diphenhydramine 50 mg IV or oral (or an equivalent histamine-1 receptor antagonist), and acetaminophen 650 mg to 1000 mg IV or oral (or an equivalent antipyretic) 1-3 hours prior to step-up dose 1, step-up dose 2, and the first treatment dose (i.e., doses within the step-up dosing schedule).
Premedication may need to be repeated for subsequent doses of teclistamab in patients who repeat doses within the step-up dosing schedule due to a treatment delay and for patients who developed CRS or ICANS after a prior dose, as described in Tables 5, 6, and 8.
Before initiating treatment with teclistamab, consider antiviral prophylaxis according to guideline recommendations to prevent herpes zoster reactivation.

Dispensing and Administration Precautions

Teclistamab is available as 10 mg/mL and 90 mg/mL concentrations; exercise caution to ensure the correct concentration is selected when calculating and preparing a dose.

REMS

Because of the risks of CRS and neurotoxicity, including ICANS, teclistamab is only available through a restricted distribution program called the Tecvayli and Talvey REMS program. Information on this REMS program is available by calling 1-855-810-8064 or at [Web].

Administration

Sub-Q Administration

Administer by sub-Q injection. Initially administered on a step-up dosing schedule (days 1, 4, and 7 of first week), followed by a once weekly dosing schedule. May reduce dosing schedule to every 2 weeks for patients who achieve and maintain a complete response or better for at least 6 months.

Must be administered by healthcare provider in setting capable of managing severe reactions (e.g., CRS, ICANS). Hospitalization required for 48 hours after all doses in step-up dosing schedule, including doses that are repeated due to treatment delays.

Preferred administration site is abdomen; may be injected into other sub-Q sites (e.g., thigh). Equally divide doses >2 mL and inject separately, at least 2 cm apart. Do not inject into damaged, tattooed, scarred, red, bruised, hard, or tender skin.

Available as 30 mg/3 mL (10 mg/mL) and 153 mg/1.7 mL (90 mg/mL) vials; do not dilute prior to administration. Use 10 mg/mL concentration for step-up doses 1 and 2, and 90 mg/mL concentration for all other doses; do not combine concentrations. May be stored in the syringe at 2–8°C or 15–30°C for up to 20 hours. Discard any unused product.

Dosage

Adults

Multiple Myeloma

Sub-Q

Step-up dosing schedule followed by weekly treatment doses as displayed in Table 1. Administer once weekly until disease progression or unacceptable toxicity occurs. May reduce dosing frequency to every 2 weeks until disease progression or unacceptable toxicity occurs for patients who achieve and maintain a complete response or better for ≥6 months.

Use actual body weight for calculations and round doses as shown in Tables 2-4.
Use 10 mg/mL concentration for step-up doses 1 and 2; use 90 mg/mL for all other doses.

Table 1: Teclistamab-cqyv Dosing Schedule1
Dosing schedule	Dose of Teclistamab
Step-up dosing schedule day 1 (step-up dose 1)	0.06 mg/kg
Step-up dosing schedule day 4 (step-up dose 2)	0.3 mg/kg (may be given 2–4 days after step-up dose 1 or up to 7 days after step-up dose 1 to allow for resolution of adverse reactions)
Step-up dosing schedule day 7 (first treatment dose)	1.5 mg/kg (may be given 2–4 days after step-up dose 2 or up to 7 days after step-up dose 2 to allow for resolution of adverse reactions)
Weekly dosing schedule (subsequent treatment doses)	1.5 mg/kg administered 1 week after first treatment dose and weekly thereafter
Biweekly dosing schedule (for patients with a complete response or better for ≥6 months)	1.5 mg/kg every 2 weeks

Table 2. Step-up Dose 1 (0.06 mg/kg) Total Dose and Injection Volume using 30 mg/3 mL (10 mg/mL) Vial1
Actual Body Weight (kg)	Total Dose (mg)	Dose Volume (mL)	Number of 30 mg/3 mL vials (10 mg/mL)
35–39	2.2	0.22	1
40–44	2.5	0.25	1
45–49	2.8	0.28	1
50–59	3.3	0.33	1
60–69	3.9	0.39	1
70–79	4.5	0.45	1
80–89	5.1	0.51	1
90–99	5.7	0.57	1
100–109	6.3	0.63	1
110–119	6.9	0.69	1
120–129	7.5	0.75	1
130–139	8.1	0.81	1
140–149	8.7	0.87	1
150–160	9.3	0.93	1
>160	Manufacturer makes no specific dosing recommendations	–	–

Table 3. Step-up Dose 2 (0.3 mg/kg) Total Dose and Injection Volume using 30 mg/3 mL (10 mg/mL) Vial1
Actual Body Weight (kg)	Total Dose (mg)	Dose Volume (mL)	Number of 30 mg/3 mL vials (10 mg/mL)
35–39	11	1.1	1
40–44	13	1.3	1
45–49	14	1.4	1
50–59	16	1.6	1
60–69	19	1.9	1
70–79	22	2.2	1
80–89	25	2.5	1
90–99	28	2.8	1
100–109	31	3.1	2
110–119	34	3.4	2
120–129	37	3.7	2
130–139	40	4	2
140–149	43	4.3	2
150–160	47	4.7	2
>160	Manufacturer makes no specific dosing recommendations	–	–

Table 4. Recommended Treatment Dose (1.5 mg/kg) Total Dose and Injection Volume using 153 mg/1.7 mL (90 mg/mL) Vial1
Actual Body Weight (kg)	Total Dose (mg)	Dose Volume (mL)	Number of 153 mg/1.7 mL vials (90 mg/mL)
35–39	56	0.62	1
40–44	63	0.7	1
45–49	70	0.78	1
50–59	82	0.91	1
60–69	99	1.1	1
70–79	108	1.2	1
80–89	126	1.4	1
90–99	144	1.6	1
100–109	153	1.7	1
110–119	171	1.9	2
120–129	189	2.1	2
130–139	198	2.2	2
140–149	216	2.4	2
150–160	234	2.6	2
>160	Manufacturer makes no specific dosing recommendations	–	–

Dosage Modification for Toxicity

May need to interrupt therapy to manage toxicities; dosage reduction not recommended. May need to repeat part or all of step-up dosing schedule in case of delay, as described in Table 5.

Table 5. Restarting Teclistamab After a Dose Delay.1
Last Administered Dose	Time Since Last Administered Dose	Actions
Step-up dose 1	>7 days	Restart step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.
Step-up dose 2	8–28 days	Repeat step-up dose 2 (0.3 mg/kg) and continue step-up dosing schedule. Administer premedications. Monitor in hospitalized setting for 48 hours.
	>28 days	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, restart step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.
Any weekly treatment dose	28 days or less	Continue at last treatment dose in weekly schedule (1.5 mg/kg once weekly; see Table 1).
	29-56 days	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, restart step-up dosing schedule at step-up dose 2 (0.3 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.
	>56 days	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, restart step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.
Any biweekly (every 2 weeks) treatment dose	63 days or less	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, continue at last treatment dose in biweekly schedule (1.5 mg/kg every 2 weeks; see Table 1).
	64-112 days	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, restart step-up dosing schedule at step-up dose 2 (0.3 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.
	>112 days	Consider benefit-risk of restarting treatment after a dose delay of >28 days due to toxicity. If benefit outweighs risk, restart step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer premedications. Monitor in hospitalized setting for 48 hours.

Cytokine Release Syndrome (CRS)

Identify CRS based on clinical presentation; evaluate and treat other causes of fever, hypoxia, and hypotension. Fever may be absent in patients with CRS due to interventions such as antipyretics or anticytokine therapy.

If CRS is suspected, withhold therapy until CRS resolves. See Table 6 and current practice guidelines for CRS management recommendations.

Intensive care may be needed. Consider laboratory monitoring for disseminated intravascular coagulation, hematology parameters, and pulmonary, cardiac, renal, and hepatic function.

Table 6. Dosage modification for Cytokine Release Syndrome (CRS)1
Grade	Presenting Symptoms	Actions
Grade 1 CRS	Temperature ≥100.4°F (38°C) attributed to CRS	Withhold therapy until CRS resolves. Administer premedications prior to next dose of teclistamab.
Grade 2 CRS	Temperature ≥100.4°F (38°C) with ≥1 of the following: Hypotension responsive to fluids and not requiring vasopressors Oxygen requirement of low-flow (≤6 L/minute) nasal cannula or blow-by	Withhold therapy until CRS resolves. Administer premedications prior to next dose of teclistamab. Monitor patient in hospitalized setting for 48 hours after next dose of teclistamab.
Grade 3 CRS	Temperature ≥100.4°F (38°C) with ≥1 of the following: Hypotension requiring one vasopressor with or without vasopressin Oxygen requirement of high-flow (>6 L/minute) nasal cannula, facemask, nonrebreather mask, or Venturi mask	First occurrence of Grade 3 CRS with duration <48 hours Withhold therapy until CRS resolves. Provide supportive therapy, which may include intensive care. Administer premedications prior to next dose of teclistamab. Monitor patient in hospitalized setting for 48 hours after next dose of teclistamab. Recurrent Grade 3 CRS or Grade 3 CRS with duration ≥48 hours Permanently discontinue therapy. Provide supportive therapy, which may include intensive care.
Grade 4 CRS	Temperature ≥100.4°F (38°C) with ≥1 of the following: Hypotension requiring multiple vasopressors (excluding vasopressin) Oxygen requirement of positive pressure (e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, mechanical ventilation)	Permanently discontinue therapy. Provide supportive therapy, which may include intensive care.

Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Withhold therapy and consider neurologic evaluation at the first sign of neurotoxicity, including ICANS. Rule out other causes of neurologic symptoms.

Intensive care may be needed. See Tables 7 and 8 for recommendations for managing non-ICANS neurotoxicity and ICANS neurotoxicity, respectively; also consider recommendations in current practice guidelines. Immune Effector Cell-Associated Encephalopathy (ICE) assessment can be used to assess the severity of ICANS and determine treatment.

Table 7. Dosage Modification for Neurotoxicity other than ICANS.1
Toxicity Type	Actions
Grade 1 neurotoxicity	Withhold therapy until neurologic symptoms resolve or stabilize.
Grade 2 or first occurrence Grade 3 neurotoxicity	Withhold therapy until neurologic symptoms improve to Grade 1 or less. Provide supportive therapy.
Recurrent Grade 3 or Grade 4 neurotoxicity	Permanently discontinue therapy. Provide supportive therapy, which may include intensive care.

Table 8. Dosage Modification for ICANS Neurotoxicity.1
Grade	Presenting Symptoms (determine management based on most severe event attributable to ICANS)	Actions
Grade 1 ICANS	Either of the following: ICE score 7-9 Depressed level of consciousness attributed to ICANS: awakens spontaneously	Withhold therapy until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medications for seizure prophylaxis.
Grade 2 ICANS	Either of the following: ICE score 3–6 Depressed level of consciousness attributed to ICANS: awakens to voice	Withhold therapy until ICANS resolves. Administer dexamethasone 10 mg (or equivalent) IV every 6 hours until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medications for seizure prophylaxis. Monitor patient in hospitalized setting for 48 hours after next dose of teclistamab.
Grade 3 ICANS	Any of the following: ICE score 0–2 Depressed level of consciousness attributed to ICANS: awakens only to tactile stimulus Any clinical seizure, focal or generalized, that resolves rapidly Nonconvulsive seizures on electroencephalogram (EEG) that resolve with intervention Raised intracranial pressure: focal/local edema on neuroimaging	First occurrence of Grade 3 ICANS Withhold therapy until ICANS resolves. Administer dexamethasone 10 mg (or equivalent) IV every 6 hours until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medications for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Monitor patient in hospitalized setting for 48 hours after next dose of teclistamab. Recurrent Grade 3 ICANS Permanently discontinue therapy. Administer dexamethasone 10 mg (or equivalent) IV every 6 hours until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medications for seizure prophylaxis. Provide supportive therapy, which may include intensive care.
Grade 4 ICANS	Any of the following: ICE score 0 Depressed level of consciousness attributed to ICANS: unarousable, requires vigorous or repetitive tactile stimuli to arouse, stupor, or coma Life-threatening prolonged seizure (>5 minutes) Repetitive clinical or electrical seizures without return to baseline in between Deep focal motor weakness such as hemiparesis or paraparesis Raised intracranial pressure or cerebral edema with signs and symptoms such as: diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing’s triad.	Permanently discontinue therapy. Administer one of the following corticosteroid regimens: dexamethasone 10 mg (or equivalent) IV every 6 hours until resolution to Grade 1 or less, then taper; or methylprednisolone 1000 mg IV once daily for 2 days or longer. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medications for seizure prophylaxis. Provide supportive therapy, which may include intensive care.

Infections

Recommended dosage modifications for infections are described in Table 9.

Table 9. Dosage Modification for Infections.1
Toxicity Type	Actions
Infection of any Grade	If active infection occurs during step-up dosing schedule, withhold therapy.
Grade 3 infection	Withhold subsequent treatment doses (i.e., doses administered after step-up dosing schedule) until infection improves to Grade 1 or less.
Grade 4 infection	Consider permanent discontinuation. If therapy is not permanently discontinued, withhold subsequent treatment doses (i.e., doses administered after step-up dosing schedule) until infection improves to Grade 1 or less.

Hematologic Toxicity

Recommended dosage modifications for hematologic adverse reactions are described in Table 10.

Table 10. Dosage Modification for Hematologic Toxicity.1
Toxicity Type	Actions
ANC <500/mm³	Withhold therapy until ANC is ≥500/mm³.
Febrile neutropenia	Withhold therapy until ANC is ≥1000/mm³ and fever resolves.
Hemoglobin <8 g/dL	Withhold therapy until hemoglobin ≥8 g/dL.
Platelet count <25,000/mm³ or Platelet count 25,000–50,000/mm³ with bleeding	Withhold therapy until platelet count ≥25,000/mm³ and no evidence of bleeding.

Other Non-Hematologic Toxicity

Recommended dosage modifications for non-hematologic adverse reactions, not addressed elsewhere, are described in Table 11.

Table 11. Dosage Modification for Other Non-Hematologic Toxicity.1
Severity	Action
Grade 3	Withhold therapy until adverse reaction improves to Grade 1 or less.
Grade 4	Consider permanent discontinuation. If therapy is not permanently discontinued, withhold subsequent treatment doses (i.e., doses administered after step-up dosing schedule) until adverse reaction improves to ≤Grade 1.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time. Patients who develop hepatotoxicity during treatment may require dose interruption or permanent discontinuation.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Obesity

Volume of distribution and clearance increase with increasing body weight. No specific dosage recommendations for patients with actual body weight >160 kg at this time.

Cautions for Teclistamab

Contraindications

None.

Warnings/Precautions

Warnings

Cytokine Release Syndrome (CRS)

Cytokine release syndrome (CRS), including life threatening or fatal CRS, can occur; 72% of patients developed CRS at recommended dosage. Follow step-up dosing schedule and administer premedications when initiating treatment to reduce risk of CRS.

Most patients developed CRS after step-up dose 1 (42%), step-up dose 2 (35%), or first treatment dose (24%). Median onset was 2 days (range: 1-6 days) after most recent dose and median duration was 2 days (range: 1-9 days).

Monitor for CRS following administration. Signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes. At the first sign of CRS, immediately evaluate patient for hospitalization and provide supportive care based on severity and current practice guidelines. Withhold teclistamab until CRS resolves; permanent discontinuation may be necessary based on severity.

Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Serious or life-threatening neurotoxicity, including ICANS, can occur.

Neurotoxicity occurred in 57% of patients at the recommended dosage; Grade 3 or 4 neurotoxicity occurred in 2.4% of patients. Most common neurotoxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). Grade 4 seizure and Guillain-Barre syndrome have occurred.

At the recommended dosage, 6% of patients developed ICANS. Most patients developed ICANS after step-up dose 1 (1.2%), step-up dose 2 (0.6%), or initial treatment dose (1.8%). Median onset of ICANS was 4 days (range: 2-8 days) after most recent dose and median duration was 3 days (range: 1-20 days). Confusional state and dysgraphia were most common manifestations of ICANS.

Monitor for signs or symptoms of neurotoxicity, including ICANS, during treatment. At the first sign of neurotoxicity (including ICANS), immediately evaluate the patient and provide supportive care based on severity and current practice guidelines. Withhold teclistamab until neurotoxicity resolves; permanent discontinuation may be necessary based on severity.

Neurotoxicity may result in CNS depression. Patients should refrain from driving or operating heavy or dangerous machinery during and for 48 hours after completion of the step-up dosing schedule. Caution advised for any new onset neurotoxicity until symptoms resolve.

Other Warnings/Precautions

Hepatotoxicity

Hepatotoxicity, sometimes fatal, reported. Elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin concentrations occurred in 34%, 28%, and 6% of patients, respectively. Grade 3 or 4 elevations in AST, ALT, and total bilirubin occurred in 1.2%, 1.8%, and 0.6% of patients, respectively. Liver enzyme elevations can occur in presence or absence of CRS.

Monitor liver enzymes and bilirubin before initiating teclistamab and as clinically indicated during treatment. May need to withhold or permanently discontinue therapy based on severity.

Infections

Severe, life-threatening, and fatal infections reported. Serious infections (including opportunistic infections) occurred in 30% of patients at recommended dosage. Grade 3 or 4 infections occurred in 35% of patients and 4.2% of patients died from infections.

Monitor for signs and symptoms of infection prior to initiating and during treatment. Administer prophylactic antimicrobials according to guideline recommendations. If infection occurs during treatment, treat according to standards of care. May need to be withhold or permanently discontinue therapy based on severity.

Monitor immunoglobulin concentrations during treatment and treat abnormalities according to guidelines; infection precautions and antibiotic or antiviral prophylaxis may be needed.

Neutropenia

Neutropenia and febrile neutropenia can occur. Decreased neutrophils occurred in 84% of patients at recommended dosage. Grade 3 or 4 neutropenia occurred in 56% of patients, and 3% of patients developed febrile neutropenia.

Monitor CBC for neutropenia at baseline and periodically during treatment. If neutropenia develops, provide supportive care and monitor for signs of infection. May need to withhold therapy based on severity of neutropenia.

Hypersensitivity and Administration Reactions

Systemic and localized administration reactions reported. May need to withhold or permanently discontinue drug based on severity of reaction.

Systemic reactions (including Grade 1 recurrent pyrexia and Grade 1 swollen tongue) occurred in 1.2% of patients at recommended dosage.

Local injection-site reactions occurred in 35% of patients at recommended dosage; 30% of reactions were Grade 1 reactions and 4.8% were Grade 2.

Immunogenicity

One patient (0.5%) in MajestTEC-1 study developed anti-teclistamab-cqyv antibodies during treatment. Due to low occurrence of anti-teclistamab-cqyv antibodies, effects on pharmacokinetics, pharmacodynamics, effectiveness, and safety are unknown.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on mechanism of action. Instruct females of reproductive potential to utilize effective contraception during treatment with teclistamab and for 5 months following final dose. Advise females who become pregnant during treatment of potential risk to fetus.

Specific Populations

Pregnancy

No adequate data in pregnant women or animals.

May cause fetal harm during pregnancy based on mechanism of action.

Lactation

Not known whether distributed into human milk or if drug has any effect on milk production or breastfed infant. Advise patients to discontinue breastfeeding during therapy and for 5 months after final dose.

Females and Males of Reproductive Potential

May cause fetal harm when administered to females during pregnancy. Verify negative pregnancy status for females of reproductive potential before initiating therapy. Advise females of reproductive potential to utilize effective contraception during treatment with teclistamab and for 5 months following the final dose.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in efficacy or safety observed between patients 65 to 74 years of age and younger patients. Insufficient data to assess efficacy and safety in patients ≥75 years of age compared to younger patients.

Hepatic Impairment

No clinically meaningful pharmacokinetic differences in patients with mild hepatic impairment (total bilirubin ≤ULN with AST >ULN or total bilirubin ≥1 to 1.5 times the ULN with any AST). Not studied in patients with moderate to severe hepatic impairment.

Renal Impairment

No clinically meaningful pharmacokinetic differences in patients with mild or moderate renal impairment (eGFR of 30 to 89 mL/minute). Not studied in patients with severe renal impairment.

Common Adverse Effects

Most common adverse reactions (≥20%): pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, diarrhea.

Most common Grade 3 to 4 laboratory abnormalities (≥20%): decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, decreased platelets.

Drug Interactions

No formal drug interaction studies performed to date. May increase exposure to cytochrome P-450 (CYP) substrates.

Drugs Metabolized by Hepatic Microsomal Enzymes

Causes cytokine release, which may suppress cytochrome P-450 (CYP) enzyme activity and increase exposure to CYP substrates. Highest risk of interaction expected from initiation of step-up dosing schedule until 7 days after first treatment dose, and during or following CRS events.

Monitor narrow therapeutic index drugs metabolized by CYP enzymes for increased serum concentrations or signs of toxicity. May need to reduce CYP substrate dosage during treatment with teclistamab.

Teclistamab Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration, mean bioavailability is 72%.

90% of steady state exposure reached after 12 weekly treatment doses.

Special Populations

Pharmacokinetics not affected by age, sex, or race.

Distribution

Mean volume of distribution is 5.63 L.

Extent

Distribution into human milk and across placenta not directly studied. Human IgG distributes to human milk and crosses placenta.

Special Populations

Volume of distribution increases with increasing body weight.

Elimination

Metabolism

Not directly studied. IgG monoclonal antibodies primarily undergo intracellular catabolism and lysosomal degradation to amino acids.

Elimination Route

Not directly studied. Renal and hepatic pathways not major elimination routes for IgG monoclonal antibodies.

Half-life

Clearance decreases over time; mean terminal elimination half-life is 27.2 days after thirteenth treatment dose.

Special Populations

Clearance increases with increasing body weight.

Stability

Storage

Parenteral

Injection

2–8°C in the original carton to protect it from light. Do not freeze or shake.

Can be stored in syringe at 2–8°C or 15–30°C for up to 20 hours.

Actions

Humanized, recombinant IgG4 derivative produced in Chinese hamster ovary cells.
Bispecific T-cell engaging antibody that binds to CD3 receptor expressed on the surface of T-cells and to B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.
Activates T-cells, causes the release of proinflammatory cytokines, and results in the lysis of multiple myeloma cells.

Advice to Patients

Discuss the signs and symptoms associated with cytokine release syndrome (CRS), including fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of CRS. Advise patients that they will be hospitalized for 48 hours after administration of all doses within the teclistamab step-up dosing schedule.
Discuss the signs and symptoms associated with neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), such as headache, confusion, dysgraphia, motor dysfunction, neuropathy, or encephalopathy. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of teclistamab step-up dosing schedule and, in the event of new onset of any neurologic toxicity symptoms, until neurologic toxicity resolves.
Teclistamab is available only through a restricted program called Tecvayli and Talvey REMS. Inform patients that they will be given a patient wallet card that they should carry with them at all times and show to all of their healthcare providers. This card describes signs and symptoms of CRS and neurologic toxicity which, if experienced, should prompt the patient to immediately seek medical attention.
Advise patients that liver enzyme elevations may occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.
Discuss the signs and symptoms of infection.
Discuss the signs and symptoms associated with neutropenia and febrile neutropenia.
Advise patients to immediately seek medical attention for any signs and symptoms of systemic administration-related reactions. Advise patients that local injection-site reactions may occur and to report any severe reactions.
Advise pregnant females to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with teclistamab and for 5 months after the last dose.
Advise females not to breastfeed during treatment with teclistamab and for 5 months after the last dose.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Because of the risks of CRS and neurotoxicity, including ICANS, teclistamab is only available through the TECVAYLI and TALVEY REMS program. Further information on the REMS program is available at [Web] or by calling 1-855-810-8064.